Incontinence

Incontinence, especially urinary, is a common condition and can have a substantial impact on quality of life. Estimates from the National Center for Health Statistics have suggested that, among noninstitutionalized persons 65 years of age and older, 44% have reported issues with urinary incontinence.^1,

Treatment

Urinary Incontinence

Injectable bulking agents are space-filling substances used to increase tissue bulk. When used to treat stress urinary incontinence, bulking agents are injected periurethrally to increase tissue bulk and thereby increase resistance to the outflow of urine. The bulking agent is injected into the periurethral tissue as a liquid that solidifies into a spongy material to bulk the urethral wall. Bulking agents may be injected over a course of several treatments until the desired effect is achieved. Periurethral bulking agents have been widely used for incontinence in women. Men have also been treated, typically those with postprostatectomy incontinence.

Key factors in determining the optimal product are biocompatibility, durability, and absence of migration. A number of periurethral bulking agents to treat urinary incontinence have been cleared for marketing by the Food and Drug Administration (FDA); however, products developed to date have not necessarily met all criteria of the ideal bulking agents. The first FDA-approved product was cross-linked collagen (eg, Contigen). The agent was found to be absorbed over time and symptoms could recur, requiring additional injections. Contigen production was discontinued in 2011. Other periurethral bulking agents cleared by FDA for urinary incontinence include carbon-coated beads (eg, Durasphere), spherical particles of calcium hydroxylapatite (CaHA) in a gel carrier (Coaptite), polydimethylsiloxane (silicone, Macroplastique), and ethylene vinyl alcohol copolymer implants (eg,Tegress, formerly Uryx). Tegresswas voluntarily removed from the market due to safety concerns.

Regulatory Status

Several periurethral bulking agents have been approved by FDA through the premarket approval process for the treatment of stress urinary incontinence due to intrinsic sphincter deficiency; other than Contigen®, approval is only for use in adult women. Products include:

• In 1993, Contigen® (Allergan), a cross-linked collagen, was approved. A supplemental approval in 2009 limited the device's indication to the treatment of urinary incontinence due to intrinsic sphincter deficiency in patients (men or women) who have shown no improvement in incontinence for at least 12 months. Allergan ceased production in 2011; no reason for discontinuation was provided publicly.
• In 1999, Durasphere® (Advanced UroScience), a pyrolytic carbon-coated zirconium oxide sphere, was approved.
• In 2004, Uryx® (CR Bard), a vinyl alcohol copolymer implant, was approved. In 2005, approval was given to market the device under the name Tegress®. In 2007, Tegress® was voluntarily removed from the market due to safety concerns.
• In 2005, Coaptite® (Merz Aesthetics, previously BioForm Medical), spherical particles of calcium hydroxylapatite, suspended in a gel carrier, was approved.
• In 2006, Macroplastique® (Cogentix Medical), polydimethylsiloxane, was approved.

• Pelvic Floor Stimulation as a Treatment of Urinary and Fecal Incontinence and Dynamic Rectal Control System as a Treatment of Fecal Incontinence (Policy #024 in the Treatment Section)
• Biofeedback (Policy #060 in the Treatment Section)
• Periureteral Bulking Agents as a Treatment of Vesicoureteral Reflux (VUR) (Policy #050 in the Surgery Section)
• Percutaneous Tibial Nerve Stimulation (Policy #069 in the Surgery Section)
• Sacral Nerve Neuromodulation/Stimulation (Policy #012 in the Treatment Section)
• Solesta (Dextranomer and Sodium Hyaluronate Gel for Submucosal Injection) (Policy #137 in the Treatment Section)

3. The use of any other periurethral bulking agent, including, but not limited to Teflon®, to treat stress urinary incontinence is considered investigational.

4. The use of periurethral bulking agents to treat urge urinary incontinence is considered investigational.


Medicare Coverage:
Per National Coverage Determination (NCD) for Incontinence Control Devices (230.10), CMS has determined that a collagen implant, and the procedure to inject it, is covered for individuals with stress urinary incontinence due to intrinsic sphincteric deficiency (ISD) when NCD 230.10 criteria is met.

The Medicare National Coverage Determination for Incontinence Control Devices (230.10) addresses collagen implants but not other types of bulking agents. Specific coverage information on collagen implants is as follows:

“Coverage of a collagen implant, and the procedure to inject it, is limited to the following types of patients with stress urinary incontinence due to ISD [intrinsic sphincteric deficiency]:
· Male or female patients with congenital sphincter weakness secondary to conditions such as myelomeningocele or epispadias;
· Male or female patients with acquired sphincter weakness secondary to spinal cord lesions;
· Male patients following trauma, including prostatectomy and/or radiation; and
· Female patients without urethral hypermobility and with abdominal leak point pressures of 100 cm H2O or less.

Patients whose incontinence does not improve with 5 injection procedures (5 separate treatment sessions) are considered treatment failures, and no further treatment of urinary incontinence by collagen implant is covered. Patients who have a recurrence of incontinence following successful treatment with collagen implants in the past (eg, 6-12 months previously) may benefit from additional treatment sessions. Coverage of additional sessions may be allowed but must be supported by medical justification.”]

For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE SNP:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

Policy Guidelines: (Information to guide medical necessity determination based on the criteria contained within the policy statements above.)

Members should have had inadequate response to conservative therapy or therapies; in general, these treatments should have been used for at least 3 months. Conservative therapy for stress incontinence includes pelvic floor muscle exercises and behavioral changes, such as fluid management and moderation of physical activities that provoke incontinence. Additional options include intravaginal estrogen therapy, use of a pessary, and treatment of other underlying causes of incontinence in members amenable to these treatments.)


[RATIONALE: The policy was created in 1997 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through June 7, 2018.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Urinary Incontinence

Clinical Context and Therapy Purpose

The purpose of injectable bulking agents in patients who have stress urinary incontinence is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does the use of injectable bulking agents improve the net health outcome in patients with stress urinary incontinence?

The following PICOTS were used to select literature to inform this review.

Patients

The relevant population of interest is patients with stress urinary incontinence.

Interventions

The therapy being considered is injectable bulking agents.

Comparators

The following therapies are currently being used to make decisions about stress urinary incontinence: conservative therapy and surgery.

Outcomes

The general outcomes of interest are symptom reduction, symptom recurrence, and treatment-related adverse events (eg, pain, infection).Bulking agents may or may not be curative, and follow-up injection may be necessary within 6 months. Beneficial effects may last between 3 and 12 months

Systematic Reviews

A Cochrane review by Kirchin et al (2012) evaluating periurethral bulking agents for urinary incontinence in women identified 14 RCTs (sample ranges, 30-355 patients) that included bulking agents in at least 1 study arm.^2,This review updated a 2007 review. All trials included women with a urodynamic diagnosis of stress incontinence, and 7 trials limited eligibility to stress incontinence due to intrinsic sphincter deficiency. The trials varied by types of bulking agent and comparator interventions used. Eight studies compared 2 bulking agents, 2 compared bulking agents with surgery, 1 compared a bulking agent with pelvic floor exercise, and one used a placebo comparison group. Several studies required that women had experienced incontinence for a specified period of time (eg, 6 or 12 months) and/or had already used conservative therapy; 1 study further specified that conservative therapy had to have been used for at least 3 months. Reviewers determined that the data were unsuitable for pooling due to heterogeneity across trials. They concluded that there was insufficient evidence to guide practice and recommended that additional RCTs with a placebo group or conservative treatment arm be conducted.

A systematic review by Davila (2011) identified 20 studies meeting inclusion criteria (prospective clinical studies or RCTs conducted among women with stress urinary incontinence [SUI] and published in English).^3, Nine studies (n=682 patients) evaluated the bulking agent cross-linked collagen. Rates of patients considered cured or improved in individual studies ranged from 21% to 81% at 12 months, 7% to 52% at 2 years, and 30% to 43% at more than 4 years. Eight trials (n=507 patients) used cross-linked polydimethylsiloxane injection. Cure rates ranged from 20% to 71% at 12 months and 18% to 40% at long-term follow-up (to 60 months). Reviewers concluded that bulking agents had demonstrated effectiveness at 1 year, but results, particularly with older agents, diminished over time and required repeated injections to restore or enhance improvement.

U.S. Food and Drug Administration-Approved Bulking Agents

Cross-Linked Collagen (Contigen)

Contigen is no longer commercially available. Previously, a clinical practice guideline (1996) for urinary continence in adults concluded that periurethral collagen is curative in 32% of men and 62% of women.^4, An RCT by Corcos et al (2005) compared the efficacy of collagen injections with surgery in 133 women.^5, Twelve-month success rates for collagen treatment (53%) were lower than for surgery (72%), but the collagen-treated group had significantly fewer adverse events (36% vs 63%, respectively).

Carbon-Coated Beads (eg, Durasphere)

A double-blind, RCT comparing carbon-coated beads with cross-linked collagen was reported by Lightner et al (2001) as part of the U.S. Food and Drug Administration (FDA)-approval process for Durasphere.^6, The trial found no difference in efficacy or in number of treatments between groups, although trial duration (12 months) might not have been sufficient to assess comparative durability.

Ethylene Vinyl Alcohol Copolymer (eg, Tegress)

Tegress, a copolymer implant, was voluntarily withdrawn from the market by its manufacturer, CR Bard, in 2007, following reports of adverse effects.^7,Tegress (formerly Uryx) had previously received FDA approval based on a trial that randomized 237 women with SUI to periurethral bulking with Uryx or to another absorbable bulking agent.^8, Efficacy at 12 months was similar between groups, with 18.4% of those receiving Uryx reporting that they were dry and 48.7% reporting improvement by 1 grade, compared with 16.5% and 53.2%, respectively, in the control group. A repeat injection was necessary for 75% of these patients to achieve satisfactory results.

Calcium Hydroxylapatite (eg, Coaptite)

Calcium hydroxylapatite (Coaptite) received FDA approval based partly on results from a single-blind randomized noninferiority comparison of collagen products among women with SUI. This trial was later published by Mayer et al (2007) and reported on 231 (78%) of 296 enrolled women.^9, For the primary outcome measure, 83 (63%) patients treated with calcium hydroxylapatite and 57 (57%) control patients treated with collagen showed an improvement of 1 grade or more on the 4-grade Stamey Urinary Incontinence Scale at 12-month follow-up. Similar results were obtained by intention-to-treat analysis, with noninferiority of calcium hydroxylapatite to collagen for improvement of at least 1 Stamey grade (58% vs 51%, respectively) and decrease in pad weight (51% vs 38%, respectively) of 50% or more.

Polydimethylsiloxane (eg, Silicone, Macroplastique)

FDA approval of polydimethylsiloxane (Macroplastique) was also partly based on a randomized noninferiority comparison with collagen in women with SUI. Results of this trial were published by Ghoneim et al (2009).^10, The trial was single-blind; patients, but not providers, were blinded. At 12 months, Macroplastique was found to be noninferior to collagen in terms of the primary efficacy variable, and improvement in the Stamey Urinary Incontinence Scale. Seventy-five (61%) of the 122 patients in the Macroplastique group and 60 (48%) of 125 patients in the collagen group improved at least 1 Stamey grade (p<0.001 for noninferiority). Twelve of the 247 randomized patients were excluded from the analysis. Two-year data on 67 of the 75 women who responded to treatment with Macroplastique were published Ghoneim et al (2010).^11, Fifty-six (84%) of the 67 patients had sustained treatment success at 24 months, defined as an improvement of at least 1 Stamey grade over baseline. Forty-five (67%) of the 67 patients evaluated at 24 months were dry (Stamey grade 0). The long-term analysis was limited because it only included a portion of responders from 1 arm of the trial. The analysis included 67 (55%) of 122 patients originally randomized to Macroplastique and did not provide data on the comparison group.

Non-FDA-Approved Bulking Agents

Dextranomer/Hyaluronic Acid (eg, Zuidex) With an Injection System (eg, Implacer)

Dextranomer/hyaluronic acid (Zuidex; AstraZeneca) with an injection system (Implacer; Q-Med AB) is used to deliver the bulking agent in the outpatient clinic setting without endoscopy. An industry-sponsored (Q-Med) randomized noninferiority trial conducted in North America compared the Zuidex system plus the Implacer with Contigen. As reported by Lightner et al (2009), patients were blinded to treatment group.^12, The primary study outcome was the proportion of women who had a 50% or greater reduction in urinary leakage on provocation testing from baseline to 12 months after the final treatment (up to 3 treatments were permitted). The primary outcome was achieved by 65% of Zuidex-treated women compared with 84% in the Contigen group; noninferiority of Zuidex was not established. The trial was limited by a high rate of missing data; primary outcomes data were missing for 35% of randomized patients.

An open multicenter study from Europe by Chapple et al (2005) reported on a 12-month 77% positive response rate (reduction ≥50% for provocation test urinary leakage) with the dextranomer/hyaluronic acid (Zuidex system with Implacer) in 142 women who met strict inclusion and exclusion criteria.^13, Similar to the North American trial, this study had a high dropout rate (24%), an unrepresentative patient population, and lacked a comparison group. Twenty-one women in this study were followed for a mean of 6.7 years after treatment with the Zuidex system.^14, At this long-term follow-up, 7 (33%) of 21 were continent, but 6 of the 7 had had other continence procedures since their Zuidex injections.

Polyacrylamide Hydrogel (eg, Bulkamid)

Randomized Controlled Trials

Polyacrylamide hydrogel (Bulkamid; Contura International A/S) is a gel containing 2.5% cross-linked polyacrylamide and 97.5% apyrogenic water. A single RCT was identified that compared Bulkamid with an FDA-approved bulking agent (Contigen).

Sokol et al (2014) reported on an RCT performed under an FDA-regulated investigational device exemption.^15, This single-blind multicenter randomized noninferiority trial compared Bulkamid with collagen gel (Contigen) in 345 women. Up to 3 injections were given. Patients completed the outcome measures at 1, 3, 6, 9, and 12 months after the last bulking procedure. The primary outcome measure was the responder rate at 12 months, determined by a composite of a 50% decrease in leakage, as measured by the 24-hour pad test, and a minimum 50% decrease in self-reported daily incontinence episodes. Bulkamid met the noninferiority margin, with a minimum 50% decrease in leakage and incontinence episodes in 53% of patients in the hydrogel group and 55% of patients in the collagen gel group. At 12 months, 47% of patients treated with hydrogel and 50% of patients treated with collagen gel reported no stress incontinence episodes.

Case Series

Several case series, conducted in Europe, have been published. The largest (N=256) is by Pai and Al-Singary (2015).^16, Women with stress or mixed urinary incontinence (>1 episode per 24 hours) who received injections of Bulkamid were assessed yearly with the quality of life measured by visual analog scale and incontinence by the International Consultation on Incontinence Questionnaire. The primary outcome was whether patients were completely dry (cured) or leaked once a week or less (significant improvement). At the 3-month follow-up, 110 (42.9%) were cured and 102 (39.8%) patients reported significant improvement. These percentages were maintained for 5 years (median, 38 months). However, only 60 (23.4%) patients were available for follow-up at 60 months, limiting interpretation of the long-term results.

A multicenter series by Lose et al (2010) included 135 adult women with symptomatic stress (n=67) or mixed (n=68) incontinence.^17, Eligibility included the presence of symptoms for at least 12 months, including at least 1 episode of incontinence daily. Ninety-eight (73%) patients completed 12-month follow-up. The primary outcome was a response to treatment, defined as patients self-reporting that they considered themselves "improved" or "cured." The response rate was 71% at 6 months and 66% at 12 months. Corresponding cure rates were 16% and 24%. There were 32 treatment-related adverse effects including 2 cases of urinary retention requiring hospitalization and 10 cases of urinary tract infection.

A 2-center prospective series by Maggiore et al (2013) included 82 women who had had stress incontinence for at least 12 months.^18, Patients received an injection of Bulkamid, and nonresponders were offered a second injection after 3 months. A total of 80 (98%) women were evaluated at 3 and 6 months, and 78 (95%) completed 1-year follow-up. The primary efficacy outcome was the subjective success rate at 1 year, defined as answering 1 or 2 on the Patient Global Improvement Impression questionnaire, which is scored from 1 (very much better) to 7 (very much worse). In an intention-to-treat analysis, the subjective success rate at 1 year was 74% (61/82 patients). Seven patients reported no change, and none reported symptom worsening. At 1 year, 87% (71/78) of patients were considered to be responders (answer of 1, 2 or 3 on the Patient Global Improvement Impression). Twenty-one (26%) patients had adverse events attributable to the injection procedure. The most common adverse event was urinary tract infection, reported by 8 patients. Four patients reported de novo urinary urgency; in all cases, this resolved by 3 months.

Eight-year outcomes were reported by Mouritsen et al (2014) for 24 women, of whom 15 (62.5%) had no further treatment, 1 received a second treatment with hydrogel, and 7 had placement of mid-urethral slings.^19, Subjectively, 44% considered their incontinence to be cured or much improved. Vaginal ultrasonography showed visible hydrogel deposits in all patients.

Polytetrafluoroethylene (eg, Teflon)

No published clinical trials were identified on polytetrafluoroethylene as a bulking agent.

Bulking Agents Not Requiring FDA Approval

Autologous Fat and Autologous Ear Chondrocytes

Other materials have been used as bulking agents but have not demonstrated the same sustained effectiveness as cross-linked collagen or carbon-coated beads. In a double-blind RCT of 56 women that compared periurethral injections of autologous fat (treatment group) with saline (placebo group), Lee et al (2001) found that periurethral fat injections were not more efficacious than placebo for treating stress incontinence.^20, At 3 months, only 6 (22.2%) of 27 patients in the treatment group and 6 (20.7%) of 29 in the placebo group were cured or improved. In addition, 1 death occurred as a result of a pulmonary fat embolism. In another clinical trial of 32 women, Bent et al (2001) reported that 50% of patients remained dry for 12 months after receiving a single outpatient injection of harvested autologous auricular cartilage.^21, While autologous substances have a nonimmunogenic advantage, their use may be limited by resorption and fibrous replacement along with local discomfort associated with harvesting procedures.

Autologous Cellular Therapy

Strasser et al (2007) published the first RCT using autologous cell therapy to treat SUI.^22, While widely cited as an important advance in the field, the Lancet retracted publication of this trial in 2008 due to ethical and quality concerns.^23,

Pooled safety data from 80 patients in 2 phase 1/2 dose-response trials from Cook MyoSite were reported by Peters et al (2014).^24, A phase 3 trial (NCT01382602) with 150 patients was completed in 2017, but trial results were not identified.

Section Summary: Urinary Incontinence

A number of RCTs and a Cochrane review of RCTs evaluating periurethral bulking agents for the treatment of urinary incontinence have been published. The trials vary by bulking agents used and comparator interventions (eg, placebo, conservative therapy, another bulking agent). Due to this heterogeneity across studies, and the small number of studies in each category, Cochrane reviewers were unable to draw specific conclusions about the efficacy of specific bulking agents compared with alternative treatments. Cross-linked collagen is the most well established bulking agent, but it was withdrawn from the market. Results from available trials have suggested that carbon-coated spheres, calcium hydroxylapatite, and polydimethylsiloxane have efficacy for treating incontinence that is similar to cross-linked collagen. For other agents (eg, autologous cellular therapy, autologous fat, autologous ear chondrocytes, Teflon), there are few RCTs and little evidence of efficacy.

Summary of Evidence

For individuals who have stress urinary incontinence who receive injectable bulking agents, the evidence includes RCTs and systematic reviews of RCTs. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Studies have shown that cross-linked collagen improves the net health outcome (ie, it is effective in some patients who have failed conservative treatment with fewer adverse events than surgery), although products that cross-link in such a way are no longer commercially available. There is evidence that the FDA-approved carbon-coated spheres, calcium hydroxylapatite, and polydimethylsiloxane have efficacy for treating incontinence, and further that they produce outcomes with a safety profile similar to cross-linked collagen. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

SUPPLEMENTAL INFORMATION

Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 4 physician specialty societies and 4 academic medical centers while this policy was under review in 2013. There was consensus agreement with all of the policy statements among reviewers who provided responses.

Practice Guidelines and Position Statements

American Urological Association et al

The 2017 joint guidelines on the surgical treatment of female stress urinary incontinence from the American Urological Association and Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction stated that bulking agents are an option for patients considering surgery for stress urinary incontinence (SUI).^25, The guidelines also stated that there are few long-term data on the efficacy of bulking agents and that retreatment is common.

European Urology Association and European Urogynaecological Association

A 2017 joint consensus review of data on implanted material for pelvic organ prolapse and SUI from the European Urology Association and European Urogynaecological Association stated: "Urethral balloons and injectables are not recommended as first-line therapy for SUI. Bulking agents are associated with lower cure rates of SUI when compared with colposuspension or autologous fascial slings."²⁶

Society of Obstetricians and Gynaecologists of Canada

The Society of Obstetricians and Gynaecologists of Canada (2010) published guidelines on the evaluation and treatment of recurrent urinary incontinence after pelvic floor surgery.^27, The guidelines recommended that conservative management be used as first-line therapy; it further stated that patients with significantly decreased urethral mobility may be managed with periurethral bulking agents as one of several treatment options.

National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence (2015) updated its guidance on urinary incontinence in women.^28, The updated guidance recommended considering "intramural bulking agents (silicone, carbon-coated zirconium beads or hyaluronic acid/dextran copolymer) for the management of stress UI [urinary incontinence] if conservative management has failed. Women should be made aware that:

• repeat injections may be needed to achieve efficacy
• efficacy diminishes with time
• efficacy is inferior to that of synthetic tapes or autologous rectus fascial slings."

The American College of Obstetricians and Gynecologists (2016) updated its practice bulletin on urinary incontinence in women.^29, The practice bulletin stated that "urethral bulking injections are a relatively noninvasive treatment for stress urinary incontinence that may be appropriate if surgery has failed to achieve adequate symptom reduction, if symptoms recur after surgery, in women with symptoms who do not have urethral mobility, or in older women with comorbidities who cannot tolerate anesthesia or more invasive surgery. However, urethral bulking agents are less effective than surgical procedures such as sling placement and are rarely used as primary treatment for stress urinary incontinence." There was insufficient evidence to recommend any specific bulking agent.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 1.

Table 1. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT02538991	TVT Versus Bulkamid®-Injections in Treatment of Stress Urinary Incontinence - Patient Satisfaction and Complications of the Treatment	212	Dec 2022

NCT: national clinical trial.

^a Denotes industry-sponsored or cosponsored trial.]
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Injectable Bulking Agents for the Treatment of Urinary Incontinence
Periurethral/Transurethral Injection of Bulking Agent for the Treatment of Urinary Incontinence
Autologous Ear Chondrocytes as Periurethral Bulking Agent
Autologous Fat as Periurethral Bulking Agent
Bulking Agents
Coaptite
Collagen Injection for Urinary Incontinence
Deflux Injectable Gel for Vesicoureteral Reflux
Durasphere
Implantation of Collagen for Urinary Incontinence
Incontinence, Urinary, Injection of Collagen for
Macroplastique
Polydimethylsiloxane (Macroplastique)
Stress Urinary Incontinence, Injection of Collagen for
Teflon, Periurethral Injection for Urinary Incontinence
Urinary Incontinence, Injection of Collagen for
Vesicoureteral Reflux, Use of Deflux Injectable Gel for
Zirconium Oxide Beads
Uryx
Ethylene Vinyl Alcohol Copolymer

References:
1. Gorina Y, Schappert S, Bercovitz A, et al. Prevalence of incontinence among older Americans. Vital Health Stat 3. Jun 2014(36):1-33. PMID 24964267.

2. Kirchin V, Page T, Keegan PE, et al. Urethral injection therapy for urinary incontinence in women. Cochrane Database Syst Rev. Feb 15 2012;2(2):CD003881. PMID 22336797.

3. Davila GW. Nonsurgical outpatient therapies for the management of female stress urinary incontinence: long- term effectiveness and durability. Adv Urol. 2011;2011:176498. PMID 21738529.

4. Agency for Health Care Policy and Research. Clinical Practice Guideline. Urinary Incontinence in Adults. Rockville, MD: Department of Health and Human Services; 1996.

5. Corcos J, Collet JP, Shapiro S, et al. Multicenter randomized clinical trial comparing surgery and collagen injections for treatment of female stress urinary incontinence. Urology. May 2005;65(5):898-904. PMID 15882720.

6. Lightner D, Calvosa C, Andersen R, et al. A new injectable bulking agent for treatment of stress urinary incontinence: results of a multicenter, randomized, controlled, double-blind study of Durasphere. Urology. Jul 2001;58(1):12-15. PMID 11445471.

7. Hurtado E, McCrery R, Appell R. The safety and efficacy of ethylene vinyl alcohol copolymer as an intra-urethral bulking agent in women with intrinsic urethral deficiency. Int Urogynecol J Pelvic Floor Dysfunct. Aug 2007;18(8):869-873. PMID 17103121.

8. Food and Drug Administration. Summary of Safety and Effectiveness: URYX Urethral Bulking Agent. 2004; https://www.accessdata.fda.gov/cdrh_docs/pdf3/P030030b.pdf. Accessed August 29, 2019.

9. Mayer RD, Dmochowski RR, Appell RA, et al. Multicenter prospective randomized 52-week trial of calcium hydroxylapatite versus bovine dermal collagen for treatment of stress urinary incontinence. Urology. May 2007;69(5):876-880. PMID 17482925.

10. Ghoniem G, Corcos J, Comiter C, et al. Cross-linked polydimethylsiloxane injection for female stress urinary incontinence: results of a multicenter, randomized, controlled, single-blind study. J Urol. Jan 2009;181(1):204- 210. PMID 19013613.

11. Ghoniem G, Corcos J, Comiter C, et al. Durability of urethral bulking agent injection for female stress urinary incontinence: 2-year multicenter study results. J Urol. Apr 2010;183(4):1444-1449. PMID 20171691.

12. Lightner D, Rovner E, Corcos J, et al. Randomized controlled multisite trial of injected bulking agents for women with intrinsic sphincter deficiency: mid-urethral injection of Zuidex via the Implacer versus proximal urethral injection of Contigen cystoscopically. Urology. Oct 2009;74(4):771-775. PMID 19660800.

13. Chapple CR, Haab F, Cervigni M, et al. An open, multicentre study of NASHA/Dx Gel (Zuidex) for the treatment of stress urinary incontinence. Eur Urol. Sep 2005;48(3):488-494. PMID 15967568.

14. Lone F, Sultan AH, Thakar R. Long-term outcome of transurethral injection of hyaluronic acid/dextranomer (NASHA/Dx gel) for the treatment of stress urinary incontinence (SUI). Int Urogynecol J. Nov 2010;21(11):1359- 1364. PMID 20571764.

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Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

51715

L8603
L8604
L8606