Percutaneous Tibial Nerve Stimulation - CAM 701106

Description
Percutaneous tibial nerve stimulation (PTNS; also known as posterior tibial nerve stimulation) is an electrical neuromodulation technique used primarily for treating voiding dysfunction. Subcutaneous tibial nerve stimulation via an implantable peripheral neurostimulator is an alternate technique for treating urgency urinary incontinence associated with overactive bladder syndrome.

Summary of Evidence
For individuals who have non-neurogenic urinary dysfunction including overactive bladder and have failed behavioral and pharmacologic therapy who receive an initial course of percutaneous tibial nerve stimulation (PTNS) , the evidence includes randomized sham-controlled trials, randomized controlled trials (RCTs) with an active comparator, and systematic reviews. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The Sham Effectiveness in Treatment of Overactive Bladder Symptoms (SUmiT) and the Overactive Bladder Innovative Therapy (OrBIT) trials are 2 key industry-sponsored RCTs. Systematic reviews that included these and other published trials have found short-term reductions in voiding dysfunction with PTNS. The largest, highest quality study was the double-blind, sham-controlled SUmiT trial, which reported a statistically significant benefit of PTNS versus sham at 12 weeks. In an additional, small sham-controlled trial, a 50% reduction in urge incontinent episodes was attained in 71% of the PTNS group compared with 0% in the sham group. The nonblinded OrBIT trial found that PTNS was noninferior to medication therapy at 12 weeks. Adverse events were limited to local irritation effects. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have overactive bladder syndrome that have failed behavioral and pharmacologic therapy who respond to an initial course of PTNS and who receive maintenance PTNS, the evidence includes observational studies and systematic reviews. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The SUmiT and OrBIT trials each included extension studies that followed individuals who responded to the initial course of PTNS and continued to receive periodic maintenance therapy. There is variability in the interval between and frequency of maintenance treatments, and an optimal maintenance regimen remains unclear. There are up to 36 months of observational data available, reporting that there is a durable effect for some of these patients. While comparative data are not available after the initial 12-week treatment period, the observational data support a clinically meaningful benefit for use in individuals who have already failed behavioral and pharmacologic therapy and who respond to the initial course of PTNS. Percutaneous tibial nerve stimulation may allow such individuals to avoid more invasive interventions. Adverse events appear to be limited to local irritation for both short- and long-term PTNS use. Typical regimens schedule maintenance treatments every 4-6 weeks. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have non-neurogenic urinary dysfunction including overactive bladder and who have failed behavioral and pharmacologic therapy or who have responded to an initial course of PTNS and then receive subcutaneous tibial nerve stimulation (STNS), the evidence includes single-arm studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The pivotal open-label, single-arm study leading to FDA-approval of the subcutaneously-implanted, wireless eCoin tibial nerve stimulation system demonstrated a 68% response rate at 48 weeks of follow-up which surpassed a performance goal of 40%. However, the certainty of the evidence is limited by the lack of comparator group and a lower response rate observed during the COVID-19 pandemic. Additionally, the FDA noted that the performance goal was identified after patients had already been implanted. An ongoing post-approval study may elucidate the certainty of benefit, including safety of reimplantation given battery lifespan concerns. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have neurogenic bladder dysfunction who receive PTNS, the evidence includes several RCTs and a systematic review of RCTs and observational data. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Only a few RCTs evaluating tibial nerve stimulation for treating neurogenic bladder have been published to date, and all but 1 performed transcutaneous stimulation rather than PTNS. Studies varied widely in factors such as study populations and comparator interventions. Study findings have not reported that tibial nerve stimulation significantly reduced incontinence symptoms and improved other outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have fecal incontinence who receive PTNS, the evidence includes several RCTs and systematic reviews. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. The available RCTs have not found a clear benefit of PTNS. None of the sham-controlled trials found that active stimulation was superior to sham for achieving a reduction in mean weekly fecal incontinence episodes. The larger sham-controlled randomized trial did find a significantly greater decrease in the absolute number of weekly incontinence episodes in the active treatment group, but the overall trial findings did not suggest the superiority of PTNS over sham treatment. An additional sham-controlled randomized trial did not identify a benefit of PTNS over sham stimulation. A meta-analysis of a single RCT and several observational studies reported that patients receiving sacral nerve stimulation experienced significant benefits compared with patients receiving PTNS. A post hoc analysis of the larger trial suggested a subset of patients with fecal incontinence (those without concomitant obstructive defecation) may benefit from PTNS. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Additional Information
2018 Input
Clinical input was sought to help determine whether the use of maintenance PTNS for individuals with non-neurogenic urinary dysfunction including overactive bladder who have failed behavioral and pharmacologic therapy and respond to an initial course of PTNS would provide a clinically meaningful improvement in the net health outcome and whether the use is consistent with generally accepted medical practice. In response to requests, clinical input was received from 3 physician respondents identified by specialty societies.

For individuals with non-neurogenic urinary dysfunction including overactive bladder who have failed behavioral and pharmacologic therapy and respond to an initial course of PTNS, clinical input supports this use provides a clinically meaningful improvement in net health outcome and indicates this use is consistent with generally accepted medical practice.

Further details from clinical input are included in the Appendix.

Background
Voiding Dysfunction
Common causes of non-neurogenic voiding dysfunction are pelvic floor neuromuscular changes (e.g., from pregnancy, childbirth, surgery), inflammation, medication (e.g., diuretics, anticholinergics), obesity, and psychogenic factors. Overactive bladder is a non-neurogenic voiding dysfunction characterized by urinary frequency, urgency, urge incontinence, and nonobstructive retention.

Neurogenic bladder dysfunction is caused by neurologic damage in patients with multiple sclerosis, spinal cord injury, detrusor hyperreflexia, or diabetes with peripheral nerve involvement. The symptoms include overflow incontinence, frequency, urgency, urge incontinence, and retention.

Treatment
Approaches to the treatment of incontinence differentiate between urge incontinence and stress incontinence. Conservative behavioral management such as lifestyle modification (e.g., dietary changes, weight reduction, fluid management, smoking cessation) along with pelvic floor exercises and bladder training are part of the initial treatment of overactive bladder symptoms and both types of incontinence. Pharmacotherapy is another option, and different medications target different symptoms. Some individuals experience mixed incontinence.

If behavioral therapies and pharmacotherapy are unsuccessful, percutaneous tibial nerve stimulation (PTNS), sacral nerve stimulation, or botulinum toxin may be recommended.

Percutaneous Tibial Nerve Stimulation
The current indication cleared by the U.S. Food and Drug Administration (FDA) for PTNS is overactive bladder and associated symptoms of urinary frequency, urinary urgency, and urge incontinence.

Altering the function of the posterior tibial nerve with PTNS is believed to improve voiding function and control. The mechanism of action is believed to be retrograde stimulation of the lumbosacral nerves (L4-S3) via the posterior tibial nerve located near the ankle. The lumbosacral nerves control the bladder detrusor and perineal floor.

Administration of PTNS consists of inserting a needle above the medial malleolus into the posterior tibial nerve followed by the application of low-voltage (10 mA, 1-10 Hz frequency) electrical stimulation that produces sensory and motor responses as evidenced by a tickling sensation and plantarflexion or fanning of all toes. Noninvasive PTNS has also been delivered with transcutaneous or surface electrodes. The recommended course of treatment is an initial series of 12 weekly office-based treatments followed by an individualized maintenance treatment schedule.

Percutaneous tibial nerve stimulation is less invasive than traditional sacral nerve neuromodulation (see evidence review 7.01.69), which has been successfully used to treat urinary dysfunction but requires implantation of a permanent device. In sacral root neuromodulation, an implantable pulse generator that delivers controlled electrical impulses is attached to wire leads that connect to the sacral nerves, most commonly the S3 nerve root that modulates the neural pathways controlling bladder function.

Percutaneous tibial nerve stimulation has also been proposed as a treatment for non-neurogenic and neurogenic bladder syndromes and fecal incontinence.

Subcutaneous Tibial Nerve Stimulation
The current indication approved by the FDA for subcutaneous tibial nerve stimulation (STNS) is urgency urinary incontinence in individuals who are intolerant or who have had an inadequate response to more conservative treatments or who have undergone a successful trial of PTNS. STNS is administered through a coin-sized leadless battery-powered implant (see Regulatory section). STNS offers a less invasive alternative to traditional sacral nerve neuromodulation and offers a convenient delivery system for automated treatments without the need for chronic outpatient PTNS treatment sessions.

Regulatory Status
In 2005, the Urgent^® PC Neuromodulation System was the initial PTNS device cleared for marketing by the FDA through the 510(k) process to treat patients suffering from urinary urgency, urinary frequency, and urge incontinence. Additional PTNS devices have been cleared for marketing through the 510(k) process. They are listed in Table 1.

The devices are not FDA cleared for other indications, such as the treatment of fecal incontinence.

Wireless technology is evolving for the treatment of overactive bladder. In March 2022, the eCoin^® Peripheral Neurostimulator System (Valencia Technologies Corporation) became the first subcutaneous tibial nerve stimulation implant approved by the FDA through the premarket authorization (PMA) process for individuals with urgency urinary incontinence (P200036; FDA Product Code: QPT).

Table 1. FDA-Cleared Percutaneous Tibial Nerve Stimulators (FDA Product Code: NAM)

Device Name	Manufacturer	Cleared	510(k)	Indications
Urgent^® PC Neuromodulation System	Uroplasty, now Cogentix Medical	Oct. 2005	K052025	Treatment of urinary urgency, urinary frequency, and urge incontinence
Urgent^® PC Neuromodulation System	Uroplasty, now Cogentix Medical	July 2006	K061333	FDA determined the 70% isopropyl alcohol prep pad contained in the kit is subject to regulation as a drug
Urgent^®PC Neuromodulation System	Uroplasty, now Cogentix Medical	Aug. 2007	K071822	Labeling update, intended use is unchanged
Urgent^® PC Neuromodulation System	Uroplasty, now Cogentix Medical	Oct. 2010	K101847	Intended use statement adds the diagnosis of overactive bladder
NURO™ Neuromodulation System	Advanced Uro-Solutions, now Medtronic	Nov. 2013	K132561	Treatment of patients with overactive bladder and associated symptoms of urinary urgency, urinary frequency, and urge incontinence
ZIDA Wearable Neuromodulation System	Exodus Innovations	March 2021	K192731	Treatment of patients with an overactive bladder and associated symptoms of urinary urgency, urinary frequency, and urge incontinence

FDA: U.S. Food and Drug Administration.

Related Policies
10117 Pelvic Floor Stimulation as a Treatment of Urinary Incontinence
20127 Biofeedback as a Treatment of Urinary Incontinence in Adults
20164 Biofeedback as a Treatment of Fecal Incontinence or Constipation
70119 Injectable Bulking Agents for the Treatment of Urinary and Fecal incontinence
70129 Percutaneous Electrical Nerve Stimulation (PENS) and Percutaneous Neuromodulation Therapy (PNT)
70169 Sacral Nerve Neuromodulation/Stimulation

Policy:
Percutaneous tibial nerve stimulation for an initial 12-week course is considered MEDICALLY NECESSARY for individuals with non-neurogenic urinary dysfunction including overactive bladder who have both:

failed behavioral therapy following an appropriate duration of 8 to 12 weeks without meeting treatment goals; and
failed pharmacologic therapy following 4 to 8 weeks of treatment without meeting treatment goals.

Maintenance therapy using monthly percutaneous tibial nerve stimulation is considered MEDICALLY NECESSARY for individuals following a 12-week initial course of percutaneous tibial nerve stimulation that resulted in improved urinary dysfunction meeting treatment goals.

Percutaneous tibial nerve stimulation is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY for all other indications, including but not limited to the following:

Neurogenic bladder dysfunction;
Fecal incontinence.

Subcutaneous tibial nerve stimulation delivered by an implantable peripheral neurostimulator system (e.g., eCoin^®) is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY for all indications, including individuals with non-neurogenic urinary dysfunction including overactive bladder.

Policy Guidelines
Individuals may be considered to have failed behavioral therapies following an appropriate duration of 8 to 12 weeks without meeting treatment goals.

Individuals may be considered to have failed pharmacologic therapies following 4 to 8 weeks of treatment without meeting treatment goals.

Annual evaluation by a physician may be performed to ensure efficacy is continuing for maintenance percutaneous tibial nerve stimulation treatments.

Coding
See the Codes table for details.

Benefit Application
BlueCard^®/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational. Therefore, FDA-approved devices may be assessed only on the basis of their medical necessity.

Rationale
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 1 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. Randomized controlled trials 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.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., people of color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (lesbian, gay, bisexual, transgender, queer, intersex, asexual); women; and people with disabilities [physical and invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Percutaneous Tibial Nerve Stimulation for Non-Neurogenic Urinary Dysfunction Including Overactive Bladder
Clinical Context and Therapy Purpose
The purpose of percutaneous tibial nerve stimulation (PTNS) in individuals who have non-neurogenic urinary dysfunction including overactive bladder (OAB) and have failed behavioral and pharmacologic therapy or those with OAB who have responded to an initial course of PTNS, is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICO was used to select literature to inform this review.

Populations
The relevant populations of interest are:

Individuals who have non-neurogenic urinary dysfunction including OAB who have failed behavioral and pharmacologic therapy, and
Individuals with OAB responsive to an initial course of PTNS.

Interventions
The therapy being considered is PTNS as an initial or maintenance therapy. During PTNS, a needle is inserted above the medial malleolus into the posterior tibial nerve followed by the application of low-voltage (10 mA, 1-10 Hz frequency) electrical stimulation. Noninvasive PTNS may be delivered with transcutaneous or surface electrodes. The recommended course of treatment is an initial series of 12 weekly office-based treatments followed by an individualized maintenance treatment schedule.

Comparators
The following therapies are currently being used to make decisions about non-neurogenic urinary dysfunction: botulinum toxin and sacral nerve stimulation (SNS).

Botulinum toxin is injected into the detrusor muscle. However, the toxin increases the risk of urinary retention and is not recommended for patients with a history of urinary retention or recurrent urinary tract infection (UTI).

Sacral nerve stimulation may be conducted in an outpatient clinical setting using temporary wire leads. Due to the incidence of lead migration, a 2-step process in a surgical setting is recommended. In the initial test phase, wire leads are inserted under the skin and if 50% improvement is reported, the patient may elect permanent implantation with a pacemaker-like stimulator. If the test phase is unsuccessful, the leads are then removed.

Outcomes
The general outcomes of interest are reductions in symptoms (e.g., self-reported assessment of symptoms, decrease in the number of voids per day) and improved quality of life. Outcomes are measured following the 12-week treatment regimen.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
Wang et al. (2020) evaluated PTNS for patients with OAB in a systematic review and meta-analysis that included 28 studies (N = 2461).¹ The efficacy of PTNS was compared to baseline information before treatment or other treatments (not specified). Reviewers included several trials discussed in the sections below: the Overactive Bladder Innovative Therapy (OrBIT) trial (Peters et al. [2009]), the Sham Effectiveness in Treatment of Overactive Bladder Symptoms (SUmiT) trial (Peters et al. [2010]), and the Finazzi-Agro et al. (2010), Vecchioli-Scaldazza et al. (2013), and Preyer et al. (2015) trials. Results demonstrated that PTNS reduced the daily frequency of the following symptoms: voiding (mean difference [MD], −2.48; 95% confidence interval [CI, −3.19 to −1.76), nocturia (MD, −1.57; 95% CI, –2.16 to −0.99), urgency episodes (MD, −2.20; 95% CI, –3.77 to −0.62), and incontinence episodes (MD, −1.37; 95% CI, –1.71 to −1.02). Percutaneous tibial nerve stimulation also improved maximum cystometric capacity (MD, 63.76; 95% CI, 31.90 to 95.61) and compliance (MD, 7.62; 95% CI, 0.61 to 14.63). The pooled success rate was 68% (95% CI, 59% to 78%). The most common complication following PTNS was pain at the puncture site.

Xiong et al. (2021) performed a systematic review with meta-analysis of 6 RCTs (N = 291) evaluating the efficacy of tibial nerve stimulation (either PTNS or transcutaneous tibial nerve stimulation [TTNS]) versus anticholinergic medications for OAB.² The SUmIT trial and trials by Vecchioli-Scaldazza et al. (2013) and Preyer et al. (2015) were among those included. There was a significant reduction in urge incontinence episodes with tibial nerve stimulation versus anticholinergic medications (MD, -1.11; 95% CI, -1.66 to -0.55). However, tibial nerve stimulation and anticholinergic medications had comparable effects on micturition, nocturia, urgency, and voided volume. Discontinuation due to adverse events was lower with tibial nerve stimulation than with anticholinergic medications (odds ratio [OR], 0.13; 95% CI, 0.03 to 0.51).

Two systematic reviews that did not include a quantitative analysis evaluated PTNS for nonobstructive urinary retention. Coolen et al. (2020) evaluated 8 studies, 5 of which reported the efficacy of PTNS and 2 of transcutaneous electrical nerve stimulation (TENS).³ The objective success rate for PTNS (defined as a decrease of at least 50% in the frequency or volume of catheterization per 24 hr) was 25% to 41%. The subjective success rate (defined as the patient's request for continued chronic treatment with PTNS) ranged from 25% to 41%. A subjective success rate of 80% was reported in 1 study of women who received transvaginal TENS. Ho et al. (2021) evaluated 16 studies, 5 of which reported on the efficacy of PTNS and 11 that of sacral neuromodulation (also referred to as SNM).⁴ The success rate for PTNS (defined as at least a 50% reduction in symptoms) ranged from 50% to 60%, while the success rates for SNM (which had variable definitions across trials) ranged between 42.5% and 100% (median, 79.2%) for the test stimulation phase and 65.5% to 100% (median, 89.1%) in the long term (median follow, 42 months).

Tutulo et al. (2018) searched the literature through December 2017 and identified 21 studies using either SNS or PTNS to treat lower urinary tract dysfunction and chronic pelvic pain not responding to standard therapies.⁵ Reviewers concluded that both SNS and PTNS were effective therapies. Percutaneous tibial nerve stimulation demonstrated higher success rates (≥ 50% reduction in leakage episodes) and fewer side effects compared with SNS; however, longer follow-up studies with PTNS are needed. Another systematic review by Tutulo et al. (2018) conducted a literature search through December 2017 of RCTs evaluating SNS and PTNS for the treatment of OAB unresponsive to standard medical therapy.⁶ Five RCTs were identified. Reviewers concluded that both SNS and PTNS, with success rates ranging from 61% to 90% and 54% to 79%, respectively, could be considered effective.

A Cochrane review by Stewart et al. (2016) evaluated electrical stimulation with nonimplanted electrodes for OAB in adults.⁷ The literature search was current up to December 2015. The objective of the review was to determine whether electrical stimulation (including vaginal and rectal electrical stimulation, and PTNS) was better than no treatment or better than any other treatment available for OAB. Studies reviewed were RCTs or quasi-RCTs of electrical stimulation that included adults with OAB with or without urgency and urge urinary incontinence. Trials whose participants had stress urinary incontinence were excluded. Sixty-three eligible trials were identified (N = 4,424 randomized participants). Reviewers included several trials discussed below: the OrBIT (Peters et al. [2009]) and OrBIT follow-up trials (MacDiarmid et al. [2010]), the SUmiT trial (Peters et al. [2010]), the Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation (STEP) trial (Peters et al. [2013]), and the Finazzi-Agro et al. (2010), Schreiner et al. (2010), Vecchioli-Scaldazza et al. (2013), and Preyer et al. (2015) trials.

Data were obtained from the end of treatment and the longest available follow-up period. The primary outcomes identified were the perception of cure, the perception of improvement, and condition-related quality of life measures as defined by the original authors or by any validated measurement scales such as the International Consultation on Incontinence Questionnaire. Secondary outcomes pertinent to the evidence review were a quantification of symptoms, procedure outcome measures, and adverse events.

The key findings from the Cochrane review (2016) of evidence are summarized in Table 2. Percutaneous tibial nerve stimulation results were combined for vaginal and rectal electrical stimulation.

Table 2. Summary of Cochrane Systematic Review Outcomes

Comparators to Electrical Stimulation^a	Electrical Stimulation Effect^a	QOE
No active treatment, placebo, or sham
Reduction in OAB symptoms	More effective	Moderate
Reduction in urge urinary incontinence	More effective	Moderate
Improvement in OAB-related quality of life	More effective	Moderate
Pelvic floor muscle training
Reduction in OAB symptoms	More effective	Moderate
Reduction in urge urinary incontinence	Effect uncertain	No evidence
Improvement in OAB-related quality of life	Effect uncertain	Low
Drug therapy
Reduction in OAB symptoms	More effective	Moderate
Reduction in urge urinary incontinence	Effect uncertain	No evidence
Improvement in OAB-related quality of life	Effect uncertain	No evidence
Oxybutynin or tolterodine
Adverse events	Lower risk	Low
Placebo/sham
Adverse events	Lower risk	Moderate

Adapted from Stewart et al. (2016).⁷
OAB: overactive bladder; QOE: quality of evidence.
^aElectrical stimulation includes percutaneous tibial nerve stimulation.

Forty-four trials did not report the primary outcomes of perception of cure or improvement in OAB. The majority of trials were deemed to be at low or unclear risk of selection and attrition bias and unclear risk of performance and detection bias. Lack of clarity regarding the risk of bias was largely due to poor reporting. Many studies did not report whether electrical stimulation was safer than other treatments or if one type of electrical stimulation was safer than others.

This review was informed by a TEC Assessment (2013) evaluating PTNS as a treatment for voiding dysfunction.⁸ It concluded that PTNS as a treatment for voiding dysfunction met TEC criteria and showed that PTNS improves the net health outcome. Specifically, PTNS ameliorated symptoms of chronic OAB or urinary voiding dysfunction, simultaneously improving quality of life parameters among patients who have failed behavioral and pharmacologic therapies.

In this assessment of 6 RCTs, TEC reviewers drew the following conclusion about the evidence:

"Evidence from randomized placebo-controlled trials supports the clinical efficacy of PTNS applied in the standard 12-week regimen. No concurrently controlled evidence exists from a trial over longer periods of time in maintenance therapy. Although the lack of controlled evidence on maintenance PTNS raises concern about whether short-term efficacy is maintained over the long term, the available 12- to 36-month evidence appears consistent with maintained efficacy in relieving symptoms of OAB and urinary voiding dysfunction. Adverse event rates, assuming accurate ascertainment, appear limited."

In 2012 and 2013, several other systematic reviews of the literature on PTNS for treating OAB were published.^9,10,11,12 Only one conducted pooled analyses of study results.⁹ This review, by Burton et al. (2012), conducted a pooled analysis of data from 4 trials (2 of which were abstracts) comparing PTNS with sham treatment. Reviewers found a significantly higher risk of successful treatment with PTNS (relative risk [RR], 7.02; 95% CI, 1.69 to 29.17) compared with a control intervention. The CI was wide, indicating a lack of precision in the pooled estimate. The patient samples in these studies were homogenous by sex, severity and duration of symptoms, and previous treatment history. The definition of successful treatment also varied among studies. The SUmiT trial (discussed below) contributed 220 (76%) of 289 patients in the pooled analysis.

Also, Shamliyan et al. (2012) conducted a comparative effectiveness review for the Agency for Healthcare Research and Quality on the broader topic of nonsurgical treatments for urinary incontinence in adult women.¹³ Reviewers identified 4 RCTs comparing PTNS with no active treatment in patients with OAB. Two of the 4 RCTs reported 12-week results of the sham-controlled SUmiT trial; 1 of them included a subgroup of SUmiT participants and was only published as an abstract. The Shamliyan report included a pooled analysis of data from 3 studies that found a statistically significant improvement in urinary incontinence in the PTNS group compared with the control group ( RR, 1.9; 95% CI, 1.1 to 3.2). This pooled analysis included 405 patients: 220 in the SUmiT trial, 150 in the SUmiT trial subgroup analysis, and 35 in a trial by Finazzi-Agro et al. (2010).¹⁴ A limit of the Shamliyan et al. (2012) analysis was that the 150 patients in the SUmiT subgroup analysis were included twice. The Shamliyan review did not discuss evidence on the efficacy of PTNS beyond 12 weeks.

Sham-Controlled Randomized Trials
The SUmiT trial, reported by Peters et al. (2010), was a sham-controlled randomized trial.¹⁵ Before conducting the trial, investigators performed a pilot study in healthy volunteers to determine the adequacy of a sham PTNS intervention.¹⁶ The sham procedure was correctly identified by 10 (33%) of 30 volunteers. This percentage is below the 50% that could be expected by chance, so investigators concluded that the procedure was a feasible sham. Eligibility criteria included: a score of 4 or more on the Overactive Bladder Questionnaire Short Form (OAB-q SF) for urgency, self-reported bladder symptoms lasting at least 3 months, and having failed conservative care for these symptoms or a diagnosis of OAB. Overactive bladder and quality of life questionnaires, as well as 3-day voiding diaries, were completed at baseline and 13 weeks.

Both the randomized sham and active intervention groups received 12 weekly 30-minute intervention sessions. In the sham group, a blunt (placebo) instrument was used to simulate the location and sensation of needle electrode insertion in active treatment. One inactive PTNS surface electrode and 2 active TENS surface electrodes were used. The TENS unit (Urgent PC system) delivered low-level stimulation to mimic the PTNS intervention. The 12-week treatment was completed by 103 (94%) of 110 in the PTNS group and 105 (95%) of 110 in the sham group.

The primary trial endpoint was an efficacy assessment measured by a 7-level global response assessment (GRA) tool, in which patients reported change in symptoms as markedly worse, moderately worse, mildly worse, the same, slightly improved, moderately improved, or markedly improved. A responder was defined as one who reported symptoms as moderately or markedly improved at week 13. The rate of responders was 54.5% (60/110) of PTNS subjects compared with 20.9% (23 of 110) of sham subjects. There was a statistically significant benefit reported with PTNS compared with sham treatment in voiding diary variables as well.

Six PTNS subjects reported 9 mild or moderate treatment-related adverse events consisting of ankle bruising, discomfort at the site of needle insertion, bleeding at the site, and tingling in the leg. No local treatment-related adverse events were reported in the sham group, and no systemic adverse events occurred in either group.

The STEP trial, an extension of the SUmiT study, included only responders from the PTNS group.¹⁷ The purpose was to determine the threshold for maintenance therapy. Of the 60 PTNS group 13-week responders, 50 entered the extension study. Patients underwent a 14-week transitional protocol consisting of 2 treatments with a 14-day interval, 2 treatments with a 21-day interval, and then 1 treatment after another 28 days. Following this 14-week period, a personal treatment plan was developed for each patient. Percutaneous tibial nerve stimulation was delivered when patients reported that their symptoms increased. Between 6 and 36 months, patients received a median of 1.1 monthly PTNS treatments after the 14-week tapering period. Data were available on 34 patients at 24 months and on 29 patients at 36 months. In a per-protocol analysis, compared with baseline, 28 (97%) of 29 patients who completed the 36-month follow-up met the primary efficacy endpoint of moderate or marked improvement in overall bladder symptoms on the GRA. Also, compared with baseline, all voiding diary measures were significantly improved in this group of patients at every 6-month follow-up.

Adverse events noted in the STEP study included 1 report of restricted vaginal opening with unknown relation to treatment and 2 mild bleeding events at the needle site in the same participant. Nine patients reported 11 mild adverse events with an unknown relation to treatment including vaginal bleeding, mild depression, shoulder pain, diarrhea, leg pain, stomach ache, pelvic pain, UTI, a pulling sensation in both feet, bladder pressure, and pinched nerve pain.

A limitation of the SUmiT trial was that the primary outcome (the GRA) is a single-item subjective measure. An additional limitation was that only short-term comparative data were available. And unlike medication that can be taken in the same manner on an ongoing basis, PTNS involves an initial 12-week course of treatment followed by maintenance therapy, which varies from the initial treatment course. To date, maintenance therapy has not been well defined.

Tables 3 and 4 summarize the SUmiT RCT and STEP extension studies.

Table 3. Summary of SUmiT RCT and STEP Extension Characteristics

Study; Trial	Countries	Sites	Dates	Randomized or Enrolled/ Completed Trial		Outcome
				PTNS	Sham
Peters et al. (2010)¹⁵; SUmiT	U.S.	23	2008 – 2009	110/103	110/105	GRA at 13 wk
Peters et al. (2013)¹⁷; STEP	U.S.	23	2009 – 2012	50/29^a	None	GRA at 36 mo

GRA: global response assessment; PTNS: percutaneous tibial nerve stimulation; RCT: randomized controlled trial; STEP: Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation; SUmiT: Sham Effectiveness in Treatment of Overactive Bladder Symptoms.
^a Extension study of 50 PTNS responders in SUmiT trial.

Table 4. Summary of SUmiT RCT and STEP Extension Results

Study	Primary Outcome: Moderately or Markedly Improved GRA
	PTNS, n/N (%)	Sham, n/N (%)	Confidence Intervals	p
SUmiT (2010)¹⁵
GRA (13 wk)	60/110 (54.5)	23/110 (20.9)	NR	< .001
STEP (2013)¹⁷
GRA (36 mo)	28/29 (97)	None	None	None

GRA: Global response assessment; NR: not reported; PTNS: percutaneous tibial nerve stimulation; RCT: randomized controlled trial; STEP: Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation: SUmiT: Sham Effectiveness in Treatment of Overactive Bladder Symptoms.

An RCT by Finazzi-Agro et al. (2010) evaluated 35 women who had urge incontinence and detrusor overactivity on urodynamic testing.¹⁴ Patients were randomized to 30-minute PTNS sessions, 3 times per week for 4 weeks (n = 18) or sham treatment (n = 17). One patient dropped out of the PTNS group, and 2 dropped out of the sham group; analysis was not intention-to-treat. The primary outcome, percent responders at 4 weeks (defined as at least 50% reduction in incontinent episodes), was attained by 12 (71%) of 17 in the PTNS group and 0 (0%) of 15 in the sham group.

Other Randomized Controlled Trials
An RCT comparing PTNS with medication for the treatment of OAB was published by Vecchioli-Scaldazza et al. (2018).¹⁸ This 3-arm trial compared solifenacin (n = 27), PTNS (n = 34), and a combination of solifenacin plus PTNS (n = 33) and followed patients through 10 months post treatment. Patients in all 3 arms experienced significant reductions from baseline in daytime frequency, night-time frequency, and urgency. Percutaneous tibial nerve stimulation was more effective than solifenacin alone, and the combination of PTNS plus solifenacin was more effective than PTNS alone. The combination therapy also showed the longest effect.

A group of RCTs has compared PTNS with an alternative treatment, medication, conservative therapy, or electrical stimulation.^{14,19,20,21,22,23,18} The trials reported inconsistent findings on short-term efficacy, and only 1 reported on the efficacy of PTNS beyond 12 weeks.

Three studies used medication as the comparison intervention. Preyer et al. (2015) published a nonblinded study comparing 12 weeks of PTNS with tolterodine in 36 women who had OAB.²¹ There were no significant differences between groups on the reduction of incontinence episodes in 24 hours (p = .89) or quality of life (p = .07).

Another RCT comparing PTNS with solifenacin was a crossover trial published by Vecchioli-Scaldazza et al. (2013).²² Forty women with OAB received PTNS (twice weekly for 6 weeks) or medication, given in random order, with a 6-week washout period between treatments. Group A received medication first, and group B received PTNS first. The primary efficacy outcome was a reduction in the number of voids in a 24-hour period. Thirty (75%) of the 40 patients completed the trial. The number of daily voids (the primary outcome) significantly decreased after each treatment compared with before treatment. Also, secondary outcomes, including nocturia urge incontinence, and voided volume, significantly improved after each treatment compared with pretreatment values. The authors did not directly compare the efficacy of medication with PTNS.

An RCT compared PTNS with conservative therapy. Schreiner et al. (2010) assessed 51 women older than 60 years of age who complained of urge urinary incontinence.²³ Women were randomized to 12 weeks of conservative treatment (Kegel exercises, bladder training) alone (n = 26) or conservative treatment plus 12 weekly sessions of PTNS (n = 25). Blinding was not discussed. The response rate at 12 weeks, defined as a reduction of at least 50% in the number of incontinence episodes reported by the patient in a bladder diary, was 76% in the PTNS group and 27% in the conservative treatment-only group (p = .001).

Gungor Ugurlucan et al. (2013) in Turkey compared transvaginal electrical stimulation (n = 38) with PTNS (n = 21) in women who had OAB.²⁰ The electrical stimulation protocol consisted of 20-minute treatments, 3 times a week for 6 to 8 weeks. Percutaneous tibial nerve stimulation was performed with an Urgent PC device used for 12 weekly, 30-minute sessions. Fifty-two (88%) of 59 patients completed the trial. The authors assessed numerous outcome variables and did not specify primary outcomes or adjust p values for multiple comparisons. Four bladder diary variables were reported. From baseline to the end of the treatment period, the groups did not differ significantly in mean change in urgency episodes, nocturia, or incontinence episodes. The mean number of urgency episodes was 2.9 at baseline and 1.6 after treatment in the electrical stimulation group, and 2.0 at baseline and 1.3 after treatment in the PTNS group (p = .54). The mean daytime frequency was 7.8 at baseline and 5.8 after treatment in the electrical stimulation group, and 7.6 at baseline and 7.4 in the PTNS group (p = .03). The authors reported that a significantly higher proportion of patients in the electrical stimulation group described themselves as cured, but they did not provide proportions or p values.

The OrBIT trial is the largest randomized trial that was not sham-controlled. This trial was a nonblinded comparison of PTNS and extended-release tolterodine (Detrol LA) in women with OAB.²⁴ Eligibility included symptoms of OAB, with at least 8 voids per 24 hours; the mean daily voids for those entering the study were 12.3. The primary outcome was the noninferiority of PTNS in the mean reduction in the number of voids per 24 hours after 12 weeks of treatment. Noninferiority was defined as no more than a 20% difference in the mean void reduction. As expected, the mean reduction in voids of 1.8 for tolterodine and 3.6 for PTNS was based on previously published efficacy data. Study findings showed the noninferiority of PTNS based on results for 84 participants.

The trial also reported on secondary outcomes. There were no statistically significant differences between the PTNS and tolterodine groups for other symptoms recorded in the voiding diary. Improvement in all OAB symptom episodes was statistically significant within each group from baseline to 12 weeks, but not between groups.

The OrBIT trial lacked blinding of patients and providers and lacked comparative data beyond the end of the initial 12-week treatment period. There was no sham or placebo group to mitigate the potential bias due to subjective outcomes. Also, the trialists did not clearly define criteria for "improvement" or "cure" (a key secondary outcome) and did not report the extent of compliance with medical therapy. Finally, different data collection methods were used in the 2 groups (e.g., for adverse event outcomes and possibly for other self-reported outcomes).

MacDiarmid et al. (2010) reported on 1-year follow-up data for patients from the OrBIT trial who had been assigned to the PTNS group and had reported symptom improvement at 12 weeks.²⁵ Of the 35 responders, 33 were included. They received a mean of 12.1 additional treatments between the 12-week and 12-month visits, and there was a median of 17 days between treatments. Data were available for 32 (97%) of the 33 participants at 6 months and 25 (76%) of the 33 participants at 12 months.

As noted, this analysis lacked data from the tolterodine group to assess long-term outcomes. Additionally, not all patients in the PTNS group were included in the follow-up analysis; rather, only PTNS responders were eligible. A potential bias is that the initial subjective outcome measure might have been subject to the placebo effect. Moreover, patients in the PTNS group who responded to initial treatment might have been particularly susceptible to a placebo response and/or might represent those with the best treatment response. Thus, these individuals might also have been susceptible to a placebo response during maintenance treatments, especially treatments offered on an as-needed basis.

Tables 5 and 6 summarize the OrBIT and OrBIT 1-year follow-up studies.

Table 5. Summary of OrBIT RCT Characteristics

Study	Countries	Sites	Dates	Randomized/Completed		Outcome^a
				PTNS	Tolterodine
Peters et al. (2009)²⁴	U.S.	11	2006 – 2008	50/41	50/43	Reported
MacDiarmid et al. (2010)²⁵ 1-y follow-up	U.S.	11	2008 – 2009	33/32^b		Reported

OrBIT: Overactive Bladder Innovative Therapy, PTNS: percutaneous tibial nerve stimulation; RCT: randomized controlled trial.
^a Mean reduction in the number of voids per 24 hours after 12 weeks of treatment.
^b Eligible responders from 12-week study.

Table 6. Summary of OrBIT RCT Results

Study	Primary Outcome: Mean Reduction in Voids per Day (SD)
OrBIT (2009)²⁴	PTNS (n = 41)		Tolterodine (n = 43)
	Baseline	12 Weeks	Baseline	12 Weeks
Voids per day	12.1 (3.1)	-2.4 (4.0)	12.5 (3.7)	-2.5 (3.9)
p		< .001		< .001
Confidence interval		NR		NR
OrBIT 1-y follow-up (2010)²⁵	PTNS (n = 25)
	Baseline	12 Months
Voids per day	12.4 (3.5)	-2.8 (3.7)	Not applicable	Not applicable
p		< .001
Confidence interval		NR

NR: not reported; OrBIT: Overactive Bladder Innovative Therapy, PTNS: percutaneous tibial nerve stimulation; RCT: randomized controlled trial; SD: standard deviation.

Section Summary: Percutaneous Tibial Nerve Stimulation for Non-Neurogenic Urinary Dysfunction Including Overactive Bladder
Initial Course of Percutaneous Tibial Nerve Stimulation
For individuals who have non-neurogenic urinary dysfunction including OAB who have failed behavioral and pharmacologic therapy and received an initial course of PTNS, a number of RCTs of PTNS have been published, including 2 key industry-sponsored RCTs, the OrBIT and SUmiT trials. Systematic reviews of the evidence have found short-term improvements with PTNS. The largest, highest quality study was the blinded, sham-controlled SUmiT trial. This trial reported a statistically significant benefit of PTNS versus sham at 12 weeks. In another small sham-controlled trial, a 50% reduction in urge incontinent episodes was attained in 71% of the PTNS group compared with 0% in the sham group. The nonblinded OrBIT trial found that PTNS was noninferior to medication treatment at 12 weeks.

Maintenance Course of Percutaneous Tibial Nerve Stimulation
For individuals who have OAB syndrome who have failed behavioral and pharmacologic therapy, respond to an initial course of PTNS, and then receive maintenance PTNS therapy, there are up to 36 months of observational data that suggest there is a durable effect for some of these patients. The SUmiT and OrBIT trials each included extension studies, which followed individuals who responded to the initial course of PTNS and continued to receive periodic maintenance therapy. There is variability in the interval between and frequency of maintenance treatments, and an optimal maintenance regimen remains unclear. While comparative data are not available after the initial 12-week treatment period, the observational data support a clinically meaningful benefit for use in individuals who have already failed behavioral and pharmacologic therapy and respond to the initial course of PTNS. Percutaneous tibial nerve stimulation may allow such individuals to avoid more invasive interventions. Adverse events appear to be limited to local irritation for both short- and long-term PTNS use. Typical regimens schedule maintenance treatments every 4 to 6 weeks.

Subcutaneous Tibial Nerve Stimulation for Non-Neurogenic Urinary Dysfunction Including Overactive Bladder
Clinical Context and Therapy Purpose
The purpose of subcutaneous tibial nerve stimulation (STNS) in individuals who have non-neurogenic urinary dysfunction including overactive bladder (OAB) with episodes of urgency urinary incontinence and have failed behavioral and pharmacologic therapy or who have responded to an initial course of PTNS, is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICO was used to select literature to inform this review.

Populations
The relevant populations of interest are:

Individuals who have non-neurogenic urinary dysfunction including OAB with episodes of urgency urinary incontinence who have failed behavioral and pharmacologic therapy, and
Individuals with OAB with episodes of urgency urinary incontinence responsive to an initial course of PTNS.

Interventions
The therapy being considered is STNS. The eCoin Peripheral Neurostimulator System is an FDA-approved coin-sized leadless battery-powered implant that delivers electrical stimulation to the tibial nerve (0.5-15 mA, 20 Hz frequency). The recommended treatment duration is 30 minutes every 3 days for the first 18 weeks (42 sessions) and every 4 days thereafter and is programmed by the clinician. A patient controller can be leveraged to inhibit an automatic session in the event of undesired or painful stimulation. The battery life is estimated at up to 3 years (range, 1 – 8 years).

Comparators
The following therapies are currently being used to make decisions about non-neurogenic urinary dysfunction: botulinum toxin and SNS.

Outcomes
The general outcomes of interest are reductions in symptoms (e.g., self-reported assessment of symptoms, decrease in the number of voids per day) and improved quality of life.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Nonrandomized Studies
Rogers et al. (2021) evaluated the safety and efficacy of the wireless eCoin device in a single-arm, open-label trial at 15 sites in the U.S.²⁶ A total of 132 patients with refractory (failed ≥ 1 second or third-line therapy) OAB received the eCoin device and were included in the intention-to-treat analysis. The majority of patients were female (98%) and 26% had received prior PTNS therapy. At 24-week follow-up, 69% (CI, 61% to 77%) of patients had a 50% reduction in urge urinary incontinence symptoms based on 3-day voiding diaries and were considered "responders." Results were similar at weeks 36 and 48 with 70% (CI, 62% to 78%) and 68% (CI, 60% to 76%) of patients responding, respectively. Fewer patients reported 100% reduction in symptoms with only 21% of patients reporting 100% response at 48 weeks. By 48 weeks there was a mean decrease in urge urinary incontinence episodes (-2.61), urinary voids (-2.12), urgency episodes (-1.49), and nocturia episodes (-0.51). Outcomes were not stratified by prior treatments received. Outcomes were impacted by the COVID-19 pandemic. Pre-pandemic and in-person responder rates were 75% and 74%, respectively, whereas the responder rate during the pandemic was 60% (n = 25) and the responder rate of remote visits was 57% (n = 14). Adverse events related to the device or procedure were reported in 20% of patients and most were mild (11%) to moderate (6%). There were 3 severe adverse events, including 1 post-operative wound infection, 1 implant site infection, and 1 device stimulation issue. While the study met its primary performance goal of at least a 40% response rate after 48 weeks of therapy, the certainty of this data is limited by the lack of blinding and a control group and the fact that a performance goal was identified after patients had already been implanted.²⁷ Thus, the FDA has required the manufacturer of the eCoin system to conduct a post-approval study to provide greater certainty of the potential benefit of the device. It is also intended to address safety concerns regarding device explantation and reimplantation following battery depletion given that the study observed the need to re-implant the device after only 1 year. Possible reasons for the negative impact of COVID-19 on the 48 week response rate were not explored.

A feasibility study conducted by MacDiarmid et al. (2019) for the eCoin device conducted in the US and New Zealand initially enrolled 46 patients at 7 sites and found reduced urge urinary incontinence episodes at 3 months follow-up (from 4.2 to 1.7 daily episodes; p = .001).²⁸ Subsequent long-term data published in 2021 indicate continued safety and efficacy of eCoin with 65% of patients considered responders and 26% of responders having complete continence at 12 months and only 1 serious infection-related adverse event.²⁹ A follow-up study of 23 patients who were reimplanted with an eCoin device after 1 year with a second-generation device found reimplantation to be successful with 74% and 82% of patients having at least 50% reduction in episodes of urge urinary incontinence at 12 and 24 weeks, respectively.³⁰ No serious device-related adverse events were reported.

Section Summary: Subcutaneous Tibial Nerve Stimulation for Non-Neurogenic Urinary Dysfunction Including Overactive Bladder
An open-label, single-arm study evaluating the first FDA-approved wireless subcutaneous tibial nerve stimulation device (eCoin) demonstrated a 68% response rate at 48 weeks of follow-up. However, the certainty of the evidence is limited by the lack of comparator group and a lower response rate during the COVID-19 pandemic. An ongoing post-approval study may elucidate the certainty of benefit, including safety of reimplantation given battery lifespan concerns.

Neurogenic Bladder Dysfunction
Clinical Context and Therapy Purpose
The purpose of PTNS in individuals who have neurogenic bladder dysfunction is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with neurogenic bladder dysfunction. Symptoms may include urinating small amounts often, problems starting urination, problems emptying the bladder, inability to detect a full bladder, and losing bladder control.

Interventions
The therapy being considered is PTNS. During PTNS, a needle is inserted above the medial malleolus into the posterior tibial nerve followed by the application of low-voltage (10 mA, 1-10 Hz frequency) electrical stimulation. Noninvasive PTNS may be delivered with transcutaneous or surface electrodes. The recommended course of treatment is an initial series of 12 weekly office-based treatments followed by an individualized maintenance treatment schedule.

Comparators
The following therapies are currently being used to make decisions about neurogenic bladder dysfunction: conservative treatments (e.g., medication to relax the bladder or to activate pelvic muscles, catheterization to empty the bladder, pelvic floor muscle training), botulinum toxin, and SNS.

Sacral nerve stimulation may be conducted in an outpatient clinical setting using temporary wire leads. Due to the incidences of lead migration, a 2-step process in a surgical setting is recommended. In the initial test phase, wire leads are inserted under the skin and if 50% improvement is reported, the patient may elect permanent implantation with a pacemaker-like stimulator. If the test phase is unsuccessful, the leads are then removed.

Outcomes
The general outcomes of interest are reduced symptoms and improved quality of life. Outcomes are measured following the 12-week treatment regimen.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
Schneider et al. (2015) published a systematic review on tibial nerve stimulation (transcutaneous and percutaneous) for treating neurogenic lower urinary tract dysfunction.³¹ In a literature search through January 2015, 16 studies were identified: 4 RCTs, 9 prospective cohort studies, 2 retrospective case series, and 1 case report. Sample sizes of the included studies were small; most included fewer than 50 patients, and none had a sample size larger than 100 patients. Three of the 4 RCTs used TTNS, and the fourth study, which was conducted in Iran, stated that PTNS was used but did not specify the device. The 4 RCTs included different study populations: women with neurogenic bladder (n = 1), men with neurogenic OAB (n = 1), multiple sclerosis patients (n = 1), and Parkinson disease patients (n = 1). Comparison interventions were tolterodine, pelvic floor muscle training, lower-limb stretching, and sham (1 study each). Pooled analyses were not conducted, and the systematic review mainly discussed intermediate outcomes (eg, maximum cystometric capacity, maximum detrusor pressure). None of the RCTs reported statistically significant between-group differences in clinical outcome variables (eg, number of episodes of urgency, frequency, nocturia).^32,33,34,35

Randomized Controlled Trials
Zonic-Imamovic et al. (2019) published the results of an RCT evaluating treatment with oxybutynin compared to TTNS in multiple sclerosis patients with OAB.³⁶ Patients were allocated to 2 groups of 30 patients each. Patients treated with anticholinergic therapy received 5 mg oxybutynin twice daily for 3 months. Patients treated with TTNS were treated at home daily for 30 minutes for 3 months. The OAB-q SF was utilized to assess the frequency of OAB symptoms and the quality of life of patients. For those treated with oxybutynin, the mean symptom subscale score improved from 61.9 ± 6.0 to 32.4 ± 14.8 (p < .001), and the mean quality of life subscale score improved from 27.8 ± 13.7 to 56.1 ± 17.3 (p < .001) after treatment. For those treated with TTNS, the mean symptom subscale score improved from 61.2 ± 14.6 to 50.8 ± 12.3 (p = .004) and the mean quality of life subscale score improved from 28.5 ± 12.6 to 38.3 ± 11.4 (p = .003). Final differences in symptoms and quality of life were found to be statistically significant between groups (p < .001) and favored treatment with oxybutynin.

A sham-controlled, double-blind RCT of TTNS in patients with neurogenic OAB and women with non-neurogenic OAB was conducted by Welk et al. (2020) from January 2016 to March 2019.³⁷ Fifty patients were recruited (OAB = 20; neurogenic = 30) and 24 were allocated to the sham group while 26 were allocated to active TTNS therapy. Baseline group characteristics were not specified but were noted to be similar. The majority of neurogenic OAB study participants had multiple sclerosis (22/30; 73%). The primary outcome measure was an improvement of patient perception of bladder condition (PPBC). Active responders did not significantly differ between groups, numbering 3/24 (13%) in the sham group and 4/26 (15%) in the active group (p = .77). No significant differences in secondary outcome measures (24-hour pad weight, voiding diary parameters, condition-specific patient-reported outcomes) were noted. The end-of-study marginal mean PPBC score was 3.3 (95% CI, 2.8 to 3.7) versus 2.9 (95% CI, 2.5 to 3.4) in the sham versus active groups, respectively. Findings were not stratified according to neurogenic or non-neurogenic disease. The authors concluded that TTNS does not appear to be effective for treating symptoms in individuals with neurogenic or non-neurogenic OAB.

Sham-controlled trials of TTNS in individuals with acute spinal cord injury (TASCI; NCT03965299 ) and Parkinson disease (UROPARKTENS; NCT02190851) are ongoing.

Section Summary: Neurogenic Bladder Dysfunction
Few RCTs evaluating tibial nerve stimulation for treating neurogenic bladder have been published to date, and all but 1 performed transcutaneous stimulation rather than PTNS. Studies varied widely in study populations and comparator interventions. Study findings have not suggested that tibial nerve stimulation significantly reduces incontinence symptoms and improves other outcomes.

Fecal Incontinence
Clinical Context and Therapy Purpose
The purpose of PTNS in individuals who have fecal incontinence is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with fecal incontinence.

Devices are not FDA cleared for the treatment of fecal incontinence.

Comparators
The following therapies are currently being used to make decisions about fecal incontinence: conservative therapies (eg, medical management, retraining of pelvic floor and abdominal wall musculature, dietary changes), medications, and SNS.

Sacral nerve stimulation may be conducted in an outpatient clinical setting using temporary wire leads. Due to the incidence of lead migration, a 2-step process in a surgical setting is recommended. In the initial test phase, wire leads are inserted under the skin, and if improvement is reported after 2 weeks, the patient may elect permanent implantation with a pacemaker-like stimulator. If the test phase is unsuccessful, the leads are then removed.

Outcomes
The general outcomes of interest are reduced symptoms (e.g., self-reported assessment of symptoms, a decrease in the number of voids per day) and improved quality of life. Outcomes are measured following the 6- to 12-week treatment regimen.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
Sarveazad et al. (2019) conducted a systematic review and meta-analysis investigating the role of tibial nerve stimulation versus sham in the control of fecal incontinence.³⁸ A literature search conducted through December 2016 identified 5 studies including 249 patients treated with PTNS and 239 treated with sham. Studies utilizing transcutaneous stimulation were also eligible. A significant decrease in the number of fecal incontinence episodes was found in the PTNS group (standardized mean difference [SMD], -0.38; 95% CI, -0.67 to 0.10; I2 = 32.8%; p = .009). However, no significant effect on incontinence scores (SMD, 0.13; 95% CI, -0.49 to 0.75; I2 = 88.0%; p = .68), resting pressure (SMD, 0.12; 95% CI, -0.14 to 0.37; I2 = 28.8%; p = .67), squeezing pressure (SMD, -0.27; 95% CI, -1.03 to 0.50; I2 = 85.5%; p = .50), or maximum tolerable volume (SMD, -0.10; 95% CI, -0.40 to 0.20; I2 = 0.0%; p = .52) was reported.

Tan et al. (2019) published a systematic review and meta-analysis reporting placebo response rates in electrical nerve stimulation trials for fecal incontinence and constipation.³⁹ A literature search was conducted through April 2017 identifying 10 randomized sham-controlled trials. Sham stimulation resulted in significant improvements in fecal incontinence episodes by 1.3 episodes per week (95% CI, -2.53 to -0.01; p = .05) and Cleveland Clinic Severity Scores by 2.2 points (95% CI, 1.01 to 3.36; p = .0003). The authors note that these findings highlight the importance of sham controls in nerve stimulation trials.

Simillis et al. (2018) conducted a systematic review and meta-analysis comparing PTNS with SNS for the treatment of fecal incontinence.⁴⁰ The literature search identified 4 studies (1 RCT, 3 nonrandomized prospective studies) including 302 patients (109 undergoing SNS, 193 undergoing PTNS). The Cochrane Collaboration's risk of bias tool was used to assess study quality. Because none of the studies blinded participants and personnel, the risk of performance and detection biases were high. Attrition and publication biases were not detected. Meta-analysis showed that patients undergoing SNS experienced significant improvements compared with patients undergoing PTNS as measured on the Wexner Fecal Incontinence Score (weighted mean difference [WMD], 2.3; 95% CI, 1.1 to 3.4) and fecal incontinence episodes per week ( WMD, 8.1; 95% CI, 4.1 to 12.1).

Edenfield et al. (2015) conducted a literature search through November 2013 and identified 17 studies (4 RCTs, 13 case series) on the use of tibial nerve stimulation (percutaneous and transcutaneous) for the treatment of fecal incontinence.⁴¹ Three of the RCTs evaluated TENS and the other PTNS. The 1 RCT and 4 case series using PTNS reported significant decreases in weekly fecal incontinence episodes following 12 weeks of treatment. The quality of life domain scores (e.g., depression, embarrassment, coping, lifestyle) showing significant improvements differed across the PTNS studies.

Horrocks et al. (2014) conducted a literature search through February 2013 and identified 12 articles, 6 related to PTNS, 5 related to transcutaneous nerve stimulation, and 1 comparing both methods.⁴² One RCT, by George et al. (2013),⁴³ discussed below, was included in the Horrocks et al. (2014) and the Edenfield et al. (2015) reviews. Horrocks et al. (2014) identified 5 case series and an RCT that reported the outcome of 50% or greater reduction in the number of fecal incontinence episodes per week immediately after PTNS treatment. In these studies, a median of 71% of patients (range, 63% – 82%) reported at least a 50% reduction in episodes. The Horrocks (2014) analysis did not report on control groups.

Randomized Controlled Trials
George et al. (2013) published the first sham-controlled trial.⁴³ Thirty patients (28 women) who had failed conservative therapy for fecal incontinence were randomized to PTNS (n = 11), TTNS (n = 11), or sham transcutaneous stimulation (n = 8). Patients in all groups received a total of 12 treatments given twice weekly for 6 weeks. (This differed from the PTNS manufacturer's recommended course of 12 weekly treatments.) The primary study endpoint was at least a 50% reduction in the mean number of incontinence episodes per week at the end of the 6-week treatment period. Only 1 patient failed to complete the trial, and data were analyzed on an intention-to-treat basis. Nine of 11 patients in the PTNS group, 5 of 11 in the TTNS group, and 1 of 8 in the sham group attained the primary endpoint (p = .035). The mean number of incontinence episodes per week (standard deviation) at the end of the study was 1.8 (0.8), 5.1 (4.2), and 4.7 (3.5) in the PTNS, transcutaneous nerve stimulation, and sham groups, respectively (p = .04). These findings are limited by the small sample size and short-term follow-up.

A large sham-controlled randomized trial, known as CONFIDeNT, was by Knowles et al. (2015).⁴⁴ The trial was double-blind and multicenter. A total of 227 patients with fecal incontinence sufficiently severe to warrant intervention (according to the principal investigator at each site) were randomized to PTNS (n = 115) or sham stimulation (n = 112). Both groups received 12 weekly, 30-minute sessions. The primary outcome was at least a 50% reduction in the mean number of episodes of fecal incontinence per week compared with baseline. The mean number of episodes was calculated from 2-week bowel diaries. Twelve patients withdrew from the trial. After treatment, 39 (38%) of 103 in the PTNS group and 32 (31%) of 102 in the sham group had at least a 50% reduction in the number of fecal incontinence episodes per week. The difference between groups was not statistically significant (adjusted odds ratio, 1.28; 95% CI, 0.72 to 2.28; p = .396). There was also no significant difference between the PTNS and sham groups in the proportion of patients achieving more than 25%, more than 75%, or 100% reduction in mean weekly episodes. There was, however, a significantly greater reduction in the absolute mean number of weekly fecal incontinence episodes in the PTNS group. The mean number of weekly fecal incontinence episodes in the PTNS group was 6.0 at baseline and 3.5 after treatment compared with 6.9 and 4.8, respectively, in the sham group ( MD, -2.26; 95% CI, -4.18 to -0.35; p = .021).

Horrocks et al. (2017) conducted a post hoc analysis of data from the CONFIDeNT trial, to evaluate factors associated with the efficacy of PTNS for fecal incontinence.⁴⁵ Results from the multivariable logistic regression on the outcome of 50% improvement in weekly fecal incontinence episodes found that age, fecal urgency, stool consistency, and severity of fecal incontinence did not affect response to PTNS. The presence of obstructive defecation was the only variable that negatively affected response to PTNS ( OR, 0.4; 95% CI, 0.2 to 0.9). Excluding patients with obstructive defecation (n = 112) resulted in a significant effect of PTNS compared with sham (49% vs 18%, p = .002).

Thin et al. (2015) published data on PTNS versus SNS for fecal incontinence.⁴⁶ Forty women were randomized, 17 to PTNS and 23 to SNS. Patients in the PTNS group had an initial course of 12 weekly sessions and received 3 maintenance treatments during the following 2 months. Sacral nerve stimulation was provided using a 2-stage approach: a test stimulation was conducted first, followed by permanent stimulation if they achieved a decrease in fecal incontinence episodes of at least 50% over the 2-week test period. The primary outcome was a reduction of at least 50% in fecal incontinence episodes per week (as determined by 2-week bowel diaries). Fifteen women passed temporary SNS and underwent permanent implantation. The proportion of patients who achieved the primary outcome at 6 months was 11 (61%) of 18 in the SNS group and 7 (47%) of 15 in the PTNS group. Rates at 3 months were 9 (47%) of 19 in the SNS group and 6 (38%) of 16 in the PTNS group. The authors did not conduct a direct statistical comparison of SNS and PTNS because the study was a pilot.

A single-center, investigator-blinded RCT compared PTNS (n = 25) to anal inserts (n = 25) in patients with fecal incontinence.⁴⁷ At 3 months, a 50% reduction in weekly episodes of fecal incontinence, as calculated by a prospectively completed 2-week bowel diary, was found in 76% (19/25) of patients in the anal insert group and 48% (12/25) of patients in the PTNS group (p = .04). Both groups had similar improvements in St Mark’s fecal incontinence scores and the International Consultation on Incontinence Questionnaire.

Zyczynski et al. (2022) conducted the Neuromodulation for Accidental Bowel Leakage (NOTABLe) sham-controlled trial of PTNS in women with fecal incontinence (N = 166).⁴⁸ Women with greater than or equal to 3 months of moderate-to-severe fecal incontinence were randomized to PTNS (n = 111) or sham stimulation (n = 55). Stimulation was delivered in 12 weekly 30-minute sessions to a single lower extremity. The primary outcome was change from baseline in St. Mark score (a 7-item, validated patient-reported outcome) measured after 12 weekly treatments. Secondary outcomes included stool consistency, bowel movement, and stool leakage episodes per week. There was no significant difference between the PTNS group (-5.3 points) and the sham group (-3.9 points) in terms of improvement from baseline in St. Mark scores (adjusted difference -1.3; 95% CI, -2.8 to 0.2). There also was no significant difference in reduction in weekly fecal incontinence episodes from baseline between the PTNS group (-2.1 episodes) and sham group (-1.9 episodes) (adjusted difference -0.26; 95% CI, -1.85 to 1.33).

Nonrandomized Studies
Sanagapalli et al. (2018) conducted a retrospective chart review of consecutive patients with multiple sclerosis-related fecal incontinence who had failed conservative therapy and who were subsequently treated with PTNS.⁴⁹ Patients (N = 33) received 8 weekly treatments of PTNS, with responders receiving an additional 4 weeks of treatment. Subjects were classified as responders based on the Wexner Fecal Incontinence Score if scores at the end of treatment were either half of the baseline score or if the score was less than 10. Twenty-six (79%) of the patients were classified as responders. Responders tended to be more symptomatic at baseline and had greater improvements in quality of life scores.

Section Summary: Fecal Incontinence
Few RCTs evaluating PTNS for the treatment of fecal incontinence have been published to date. The available RCTs have not found a clear benefit of PTNS. None of the sham-controlled trials found that active stimulation was superior to sham for achieving a reduction in mean incontinence episodes. The sham-controlled randomized trial by Knowles et al. found a significantly greater decrease in the absolute number of weekly incontinence episodes in the active treatment group, but the overall trial findings did not suggest the superiority of PTNS over sham treatment. The sham-controlled randomized trial by Zyczynski et al. did not indicate a benefit of PTNS over sham stimulation either. A meta-analysis of 1 RCT and several observational studies reported that patients receiving SNS experienced significant benefits compared with patients receiving PTNS. A post hoc analysis of the larger trial suggested a subset of patients with fecal incontinence, those without concomitant obstructive defecation, might benefit from PTNS.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

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.

2018 Input
Clinical input was sought to help determine whether the use of maintenance percutaneous tibial nerve stimulation (PTNS) for individuals with non-neurogenic urinary dysfunction including overactive bladder who have failed behavioral and pharmacologic therapy and respond to an initial course of PTNS would provide a clinically meaningful improvement in the net health outcome and whether the use is consistent with generally accepted medical practice. In response to requests, clinical input was received from 3 physician respondents identified by specialty societies.

Further details from clinical input are included in the Appendix.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in Supplemental Information if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American Urological Association et al.
In 2019, the American Urological Association and the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction published updated guidelines on the diagnosis and treatment of non-neurogenic overactive bladder in adults.⁵⁰ The guidelines included a statement that clinicians may offer PTNS as a third-line treatment option in carefully selected patients. The statement carried a grade C rating, indicating that the balance of benefits and risks/burdens are uncertain.

American College of Obstetricians and Gynecologists
In 2015, the American College of Obstetricians and Gynecologists practice bulletin on the treatment of urinary incontinence in women did not address PTNS or other types of nerve stimulation.⁵¹

American Gastroenterological Association
In 2017, the American Gastroenterological Association issued an expert review and clinical practice update on surgical interventions and device-aided therapy for the treatment of fecal incontinence.⁵² The update stated that "until further evidence is available, percutaneous tibial nerve stimulation should not be used for managing FI [fecal incontinence] in clinical practice."

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 7.

Table 7. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT05685433^a	A Real World Study of eCoin for Urgency Urinary Incontinence: Post Approval Evaluation (RECIPE)	200	Dec 2030 (recruiting)
NCT03965299	Transcutaneous Tibial Nerve Stimulation in Patients With Acute Spinal Cord Injury to Prevent Neurogenic Detrusor Overactivity: A Nationwide Randomised, Sham-controlled, Double-blind Clinical Trial (TASCI)	114	Sep 2025 (recruiting)
NCT05882318^a	Evaluating Effectiveness of Sensory and Subsensory Stimulation Amplitudes With eCoin® Tibial Nerve Stimulation in Urgency Urinary InContinence Episodes and Quality of Life (ESSENCE)	50	Jul 2024 (recruiting)
NCT05422625	PTNS for Female Patients Suffering From Multiple Sclerosis (PTNS-MS)	34	Oct 2023
NCT02873312	Prospective, Multi-Center, Randomized, Double-Blinded Trial of Percutaneous Tibial Nerve Stimulation With the Bioness StimRouter Neuromodulation System Versus Sham in the Treatment of Overactive Bladder (OAB)	180	Jul 2021 (status unknown )
Unpublished
NCT02190851	Evaluation of Treatment by Transcutaneous Electrical Nerve Stimulation (TENS) of the Posterior Tibial Nerve for Lower Urinary Tract Disorders in Parkinson's Syndrome (UROPARKTENS)	220	Oct 2020 (completed)

NCT: national clinical trial.

References:

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Coolen RL, Groen J, Scheepe JR, et al. Transcutaneous Electrical Nerve Stimulation and Percutaneous Tibial Nerve Stimulation to Treat Idiopathic Nonobstructive Urinary Retention: A Systematic Review. Eur Urol Focus. Sep 2021; 7(5): 1184-1194. PMID 33268327
Ho FCS, He C, Yao HH, et al. Efficacy of sacral neuromodulation and percutaneous tibial nerve stimulation in the treatment of chronic nonobstructive urinary retention: A systematic review. Neurourol Urodyn. Jun 2021; 40(5): 1078-1088. PMID 33973670
Tutolo M, Ammirati E, Heesakkers J, et al. Efficacy and Safety of Sacral and Percutaneous Tibial Neuromodulation in Non-neurogenic Lower Urinary Tract Dysfunction and Chronic Pelvic Pain: A Systematic Review of the Literature. Eur Urol. Mar 2018; 73(3): 406-418. PMID 29336927
Tutolo M, Ammirati E, Van der Aa F. What Is New in Neuromodulation for Overactive Bladder?. Eur Urol Focus. Jan 2018; 4(1): 49-53. PMID 29773501
Stewart F, Gameiro LF, El Dib R, et al. Electrical stimulation with non-implanted electrodes for overactive bladder in adults. Cochrane Database Syst Rev. Dec 09 2016; 12: CD010098. PMID 27935011
Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Percutaneous tibial nerve stimulation for the treatment of voiding dysfunction. TEC Assessments. 2013;Volume 28:Tab 10. PMID
Burton C, Sajja A, Latthe PM. Effectiveness of percutaneous posterior tibial nerve stimulation for overactive bladder: a systematic review and meta-analysis. Neurourol Urodyn. Nov 2012; 31(8): 1206-16. PMID 22581511
Levin PJ, Wu JM, Kawasaki A, et al. The efficacy of posterior tibial nerve stimulation for the treatment of overactive bladder in women: a systematic review. Int Urogynecol J. Nov 2012; 23(11): 1591-7. PMID 22411208
Moossdorff-Steinhauser HF, Berghmans B. Effects of percutaneous tibial nerve stimulation on adult patients with overactive bladder syndrome: a systematic review. Neurourol Urodyn. Mar 2013; 32(3): 206-14. PMID 22907807
Gaziev G, Topazio L, Iacovelli V, et al. Percutaneous Tibial Nerve Stimulation (PTNS) efficacy in the treatment of lower urinary tract dysfunctions: a systematic review. BMC Urol. Nov 25 2013; 13: 61. PMID 24274173
Shamliyan T, Wyman J, Kane RL. Nonsurgical Treatments for Urinary Incontinence in Adult Women: Diagnosis and Comparative Effectiveness (Comparative Effectiveness Review No. 36). Rockville, MD: Agency for Healthcare Research and Quality; 2012.
Finazzi-Agro E, Petta F, Sciobica F, et al. Percutaneous tibial nerve stimulation effects on detrusor overactivity incontinence are not due to a placebo effect: a randomized, double-blind, placebo controlled trial. J Urol. Nov 2010; 184(5): 2001-6. PMID 20850833
Peters KM, Carrico DJ, Perez-Marrero RA, et al. Randomized trial of percutaneous tibial nerve stimulation versus Sham efficacy in the treatment of overactive bladder syndrome: results from the SUmiT trial. J Urol. Apr 2010; 183(4): 1438-43. PMID 20171677
Peters K, Carrico D, Burks F. Validation of a sham for percutaneous tibial nerve stimulation (PTNS). Neurourol Urodyn. 2009; 28(1): 58-61. PMID 18671297
Peters KM, Carrico DJ, Wooldridge LS, et al. Percutaneous tibial nerve stimulation for the long-term treatment of overactive bladder: 3-year results of the STEP study. J Urol. Jun 2013; 189(6): 2194-201. PMID 23219541
Vecchioli-Scaldazza C, Morosetti C. Effectiveness and durability of solifenacin versus percutaneous tibial nerve stimulation versus their combination for the treatment of women with overactive bladder syndrome: a randomized controlled study with a follow-up of ten months. Int Braz J Urol. Jan-Feb 2018; 44(1): 102-108. PMID 29064651
Boudaoud N, Binet A, Line A, et al. Management of refractory overactive bladder in children by transcutaneous posterior tibial nerve stimulation: A controlled study. J Pediatr Urol. Jun 2015; 11(3): 138.e1-10. PMID 25979217
Gungor Ugurlucan F, Onal M, Aslan E, et al. Comparison of the effects of electrical stimulation and posterior tibial nerve stimulation in the treatment of overactive bladder syndrome. Gynecol Obstet Invest. 2013; 75(1): 46-52. PMID 23171636
Preyer O, Umek W, Laml T, et al. Percutaneous tibial nerve stimulation versus tolterodine for overactive bladder in women: a randomised controlled trial. Eur J Obstet Gynecol Reprod Biol. Aug 2015; 191: 51-6. PMID 26073262
Vecchioli-Scaldazza C, Morosetti C, Berouz A, et al. Solifenacin succinate versus percutaneous tibial nerve stimulation in women with overactive bladder syndrome: results of a randomized controlled crossover study. Gynecol Obstet Invest. 2013; 75(4): 230-4. PMID 23548260
Schreiner L, dos Santos TG, Knorst MR, et al. Randomized trial of transcutaneous tibial nerve stimulation to treat urge urinary incontinence in older women. Int Urogynecol J. Sep 2010; 21(9): 1065-70. PMID 20458465
Peters KM, Macdiarmid SA, Wooldridge LS, et al. Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial. J Urol. Sep 2009; 182(3): 1055-61. PMID 19616802
MacDiarmid SA, Peters KM, Shobeiri SA, et al. Long-term durability of percutaneous tibial nerve stimulation for the treatment of overactive bladder. J Urol. Jan 2010; 183(1): 234-40. PMID 19913821
Rogers A, Bragg S, Ferrante K, et al. Pivotal Study of Leadless Tibial Nerve Stimulation with eCoin® for Urgency Urinary Incontinence: An Open-Label, Single Arm Trial. J Urol. Aug 2021; 206(2): 399-408. PMID 33797291
U.S. Food and Drug Administration. Summary of Safety and Effectiveness Data (SSED): eCoin Peripheral Neurostimulator System (P200036). March 1, 2022; https://www.accessdata.fda.gov/cdrh_docs/pdf20/P200036B.pdf. Accessed June 28, 2023.
MacDiarmid S, Staskin DR, Lucente V, et al. Feasibility of a Fully Implanted, Nickel Sized and Shaped Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome with Urgency Urinary Incontinence. J Urol. May 2019; 201(5): 967-972. PMID 31009968
Gilling P, Meffan P, Kaaki B, et al. Twelve-month Durability of a Fully-implanted, Nickel-sized and Shaped Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome with Urgency Urinary Incontinence: A Single-Arm, Prospective Study. Urology. Nov 2021; 157: 71-78. PMID 34048826
Kaaki B, English S, Gilling P, et al. Six-Month Outcomes of Reimplantation of a Coin-Sized Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome With Urgency Urinary Incontinence. Female Pelvic Med Reconstr Surg. May 01 2022; 28(5): 287-292. PMID 35536667
Schneider MP, Gross T, Bachmann LM, et al. Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review. Eur Urol. Nov 2015; 68(5): 859-67. PMID 26194043
Monteiro ES, de Carvalho LB, Fukujima MM, et al. Electrical stimulation of the posterior tibialis nerve improves symptoms of poststroke neurogenic overactive bladder in men: a randomized controlled trial. Urology. Sep 2014; 84(3): 509-14. PMID 25168524
Perissinotto MC, D'Ancona CA, Lucio A, et al. Transcutaneous tibial nerve stimulation in the treatment of lower urinary tract symptoms and its impact on health-related quality of life in patients with Parkinson disease: a randomized controlled trial. J Wound Ostomy Continence Nurs. Jan-Feb 2015; 42(1): 94-9. PMID 25549314
Gaspard L, Tombal B, Opsomer RJ, et al. [Physiotherapy and neurogenic lower urinary tract dysfunction in multiple sclerosis patients: a randomized controlled trial]. Prog Urol. Sep 2014; 24(11): 697-707. PMID 25214451
Eftekhar T, Teimoory N, Miri E, et al. Posterior tibial nerve stimulation for treating neurologic bladder in women: a randomized clinical trial. Acta Med Iran. 2014; 52(11): 816-21. PMID 25415813
Zonić-Imamović M, Imamović S, Čičkušić A, et al. Effects of Treating an Overactive Urinary Bladder in Patients with Multiple Sclerosis. Acta Med Acad. Dec 2019; 48(3): 271-277. PMID 32124625
Welk B, McKibbon M. A randomized, controlled trial of transcutaneous tibial nerve stimulation to treat overactive bladder and neurogenic bladder patients. Can Urol Assoc J. Jul 2020; 14(7): E297-E303. PMID 32017693
Sarveazad A, Babahajian A, Amini N, et al. Posterior Tibial Nerve Stimulation in Fecal Incontinence: A Systematic Review and Meta-Analysis. Basic Clin Neurosci. 2019; 10(5): 419-431. PMID 32284831
Tan K, Wells CI, Dinning P, et al. Placebo Response Rates in Electrical Nerve Stimulation Trials for Fecal Incontinence and Constipation: A Systematic Review and Meta-Analysis. Neuromodulation. Dec 2020; 23(8): 1108-1116. PMID 31889364
Simillis C, Lal N, Qiu S, et al. Sacral nerve stimulation versus percutaneous tibial nerve stimulation for faecal incontinence: a systematic review and meta-analysis. Int J Colorectal Dis. May 2018; 33(5): 645-648. PMID 29470730
Edenfield AL, Amundsen CL, Wu JM, et al. Posterior tibial nerve stimulation for the treatment of fecal incontinence: a systematic evidence review. Obstet Gynecol Surv. May 2015; 70(5): 329-41. PMID 25974730
Horrocks EJ, Thin N, Thaha MA, et al. Systematic review of tibial nerve stimulation to treat faecal incontinence. Br J Surg. Apr 2014; 101(5): 457-68. PMID 24446127
George AT, Kalmar K, Sala S, et al. Randomized controlled trial of percutaneous versus transcutaneous posterior tibial nerve stimulation in faecal incontinence. Br J Surg. Feb 2013; 100(3): 330-8. PMID 23300071
Knowles CH, Horrocks EJ, Bremner SA, et al. Percutaneous tibial nerve stimulation versus sham electrical stimulation for the treatment of faecal incontinence in adults (CONFIDeNT): a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial. Lancet. Oct 24 2015; 386(10004): 1640-8. PMID 26293315
Horrocks EJ, Chadi SA, Stevens NJ, et al. Factors Associated With Efficacy of Percutaneous Tibial Nerve Stimulation for Fecal Incontinence, Based on Post-Hoc Analysis of Data From a Randomized Trial. Clin Gastroenterol Hepatol. Dec 2017; 15(12): 1915-1921.e2. PMID 28647458
Thin NN, Taylor SJ, Bremner SA, et al. Randomized clinical trial of sacral versus percutaneous tibial nerve stimulation in patients with faecal incontinence. Br J Surg. Mar 2015; 102(4): 349-58. PMID 25644291
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Coding Section

Codes	Number	Description
CPT	64566	Posterior tibial neurostimulation, percutaneous needle electrode, single treatment, includes programming
	0816T(effective 01/01/2024)	Open insertion or replacement of integrated neurostimulation system for bladder dysfunction including electrode(s) (e.g., array or leadless), and pulse generator or receiver, including analysis, programming, and imaging guidance, when performed, posterior tibial nerve; subcutaneous
	0818T(effective 01/01/2024)	Revision or removal of integrated neurostimulation system for bladder dysfunction, including analysis, programming, and imaging, when performed, posterior tibial nerve; subcutaneous
HCPCS	No specific codes
ICD-10-CM	N32.81	Overactive bladder
	N39.41 – N39.498	Other specified urinary incontinence code range
	R33.0 – R33.9	Retention of urine code range
	R35.0	Frequency of micturition
	R35.81	Nocturnal polyuria
	R35.89	Other polyuria
	R39.15	Urgency of urination
	R15.0 – R15.9	Fecal incontinence code range
ICD-10-PCS		ICD-10-PCS codes are only used for inpatient services.
	01HY3MZ	Surgical, peripheral nervous system, insertion, peripheral nerve, percutaneous, neurostimulator lead
Type of service	Surgery
Place of service	Inpatient/Outpatient

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

History From 2013 Forward

01/04/2024	Annual review. Updating description, policy, background, rationale and references. No other changes.
12/11/2023	Adding CPT codes 0816T and 0818T to policy effective date is 01/01/2024.
01/09/2023	Annual review, no change to policy intent. Updating coding, rationale, and references.
01/10/2022	Annual review, no change to policy intent. Updating description, regulatory status, rationale and references.
01/01/2021	Annual review, no change to policy intent. Updating guidelines, coding, rationale and references.
01/14/2020	Annual review, no change to policy intent. Updating rationale, references, background and description.
01/29/2019	Annual review, updating medical necessity to include use of PTNS in OAB syndrome that has failed behavioral and pharmacologic therapy. Also updating, background, description, regulatory status, guidelines, rationale, references and coding.
01/03/2018	Annual review, no change to policy intent.
01/17/2017	Annual review, no change to policy intent. Updating rationale and references.
01/28/2016	Annual review, no change to policy intent. Updating background, description, guidelines rationale and references.
02/02/2015	Annual review, added verbiage to indicate use of this technology for fecal incontinence is investigational. Changed title to Percutaneous Tibial Nerve Stimulation. Added policy guidelines and coding. Updating desdcription, background, regulatory status, rationale and references.
02/10/2014	Annual Review. Added regulatory status, related policies. Updated rationale and references. Deleted duplicative language. No change in policy intent.

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Percutaneous Tibial Nerve Stimulation - CAM 701106