Rethinking the artificial urinary sphincter : from current knowledge to the development of a new smart device

Abstract

Background: Urinary incontinence (UI) plagues millions of women and men worldwide, leading to social stigma, low self-esteem, poor quality of life, and affects their loved ones. In women, frequent causes include childbirth, and in men prostate surgery for benign or malignant disease. In both genders congenital anomalies, neurological diseases, pelvic surgery, and radiation therapy are incriminating factors. Many patients struggle daily with pads and/or diapers, often unaware of the existence of a surgical cure. Since the seventies, the AMS 800Ô (Boston Scientific - Marlborough, Massachusetts, USA) artificial urinary sphincter (AUS) has been the reference to treat severe male stress UI (SUI) secondary to intrinsic sphincter deficiency (ISD). In women, it constitutes a second-line option, the mid-urethral sling (MUS) being recommended as first-line surgical therapy in moderate to severe cases. However, although efficient, it has several drawbacks, namely poor ergonomics, untailored status to patients’ physical activities, high revision and explantation rates.

Aims: To solve the above issues, a novel electronic AUS was incepted in France in 2007. This thesis tells the modern developmental journey of this device for severe SUI treatment. The objective is three- fold: to conduct a review of the current AMSÔ in both genders to identify potential literature gaps to identify and analyze data resulting from bench tests and clinical studies, and to conduct pre-clinical feasibility, performance and safety studies on human cadavers and animals prior to FIM studies. The 6 constituent papers present the results of the process rethinking the current AMS 800Ô known today, from State of the Art (papers I-III) to the design stages (paper IV) and subsequent pre-clinical implantation phases (papers V and VI) prior to the First in Man study, which eventually leads to the obtention of CE marking.

Material, Methods, and Results: In Paper I, a systematic literature review of AMS 800Ô implantation in women with non-neurogenic severe SUI, non-extant to date, was performed. The 12 articles included showed a very low level of evidence, result heterogeneity in performance and safety outcomes and highlighted the need for post- market studies. Paper II addressed the absence of standardized continence outcome measurement tool, essential to homogenize functional reported outcomes data, but also crucial for defining the primary outcomes of the FIM study. We retrospectively assessed the 24- hour pad weight test in 180 men treated with primary AUS for PPUI. Secondarily, its correlation to quality-of-life was analyzed. Thirdly (Paper III), we retrospectively evaluated long-term continence and safety results of transscrotal versus transperineal (TP) primary AUS implantation in 183 men with PPUI in a single center. No statistical difference in performance outcomes was seen; however, the TP technique appeared to present worse long-term safety results. In Paper IV, we dimensioned the novel AUS by prospectively measuring the exact in vivo volume taken by the AMS 800Ô occlusive cuff after its pressurization at implantation. We found that the larger the cuff, the greater the accommodated volume, which did not surpass 1 cc. Therefore, the final prototype could be designed, an essential developmental milestone. In paper V the usability and performance of the novel AUS was established, in accordance with current FDA and European regulations on AIMDs in development. The device’s usability and performance were shown in 8 anatomical subjects, using randomly obtained urodynamic maximum urethral closure pressure ranges, equivalent to those of the AMS 800Ô. In Paper VI, we ascertained the novel device’s feasibility of implantation and histopathological safety in an animal pilot study using two wether models. The study showed the suitability of the models, the device’s ease of implantation and the absence of peri-or postoperative, and histopathological adverse events. We could therefore safely consider a Pivot study.

Conclusion: Developing a novel AUS is a lengthy, expensive, and regulatory challenging process. In the ‘State of the Art’, essential to assess the ‘Gold standard’, we identified three literature gaps relevant for the risk analysis and evaluated similar competing devices. We showed a fine example of the application of ‘in vivo’ clinical study to the design of the smart AUS device. These initiated the required pre- clinical studies prior to FIM trials, demonstrating device feasibility, performance, and safety. the importance of post-market studies was also highlighted, and we strive to soon deliver a safe and efficient electronic device, tailored to the patient’s needs, whilst abiding to current regulations.