The aim of this study was three-fold: I. To describe the implantation ratio, the true success ratio, the false positive ratio and the subjective success ratio at 12 months follow-up in patients who received sacral neuromodulation (SNM) therapy.  II. To explore differences in outcomes between true (TP) and false positive cases (FP). III. To examine the effect of SNM on the 24 hours diuresis and explore the potential role of diuresis as a surrogate variable to detect a potential placebo effect.

Between March 2018 and December 2021 a multidisciplinary single centre prospective study was held. Patients from the Urology and Colorectal surgery department with therapy resistant pelvic floor disorders who were planned for a SNM 2-staged tined lead procedure with the Interstim II ® were enrolled. According to the current practice, the decision to proceed from Stage I (the first stage tined lead procedure) to Stage II (the definitive implantation), i.e. positive advice, was made at the control visit during the test period by the treating physician. The duration of the testphase varied from 2 to 4 weeks depending on the indication of therapy. 
The evaluation was accomplished based on a quick, rather intuitive screening for changes in bladder and bowel diary parameters and on the anamnesis of patient satisfaction. As a quality control on the physician’s advice for implant, a mathematical re-analysis of bladder and bowel diaries was performed after the control visit by the researcher. 
Both bladder and bowel diaries were collected at baseline at during the testphase. Also symptom specific patient reported outcome measures (PROMS) (i.e. the Urological symptom (US) satisfaction score and the Bowel  Symptom (BS) satisfaction score, both rated from 0 to 100% satisfaction) were completed. Objective success was defined as ≥ 50% improvement in for urological patients and as ≥ 50% improvement in one or more of the bothersome bowel symptoms for the colorectal surgery patients. Subjective success was assessed by the Patient Global Impression of Change score (PGIC) during the testphase and at 1, 6 and 12 months follow-up after stage II. A PGIC score of ≥ 5/7 (from 5 ‘moderately better and a slight but noticeable change’ to 7 ‘A great deal better, and a considerable improvement that has made all the difference’) was  considered as having subjective success. 
Independently from the advice of the physician, the true success ratio, i.e. having both objective success and subjective success during the testphase, was determined by the researcher.  False positives were defined as the  patients who did not show sustained therapeutic subjective success, i.e. a PGIC score < 5, despite having shown true success during the test phase. True positives were defined as patients who had true success during the testphase and did show sustained subjective success  (PGIC ≥ 5) 1 month after stage II. Outcomes were compared between FP and TP. Descriptive statistics using SPSS version 25.0 were performed.

I. The implantation, true success and FP ratios were 76/93 (82%), 71/93 (76%) and 16% (11/67) %, respectively. Implantation ratios for the Urology department (53/65) and the Colorectal surgery department (23/28) were both 82%. After re-assessment 68 patients were correctly implanted, 14 cases were correctly refused, 8 cases were incorrectly implanted, and 3 cases were incorrectly refused. Four of the 8 incorrectly implanted cases did not show objective success on urological symptoms, but they did show objective success on bowel symptoms. The subjective success ratio for the total group at twelve months follow-up was 35/40 (87,5%).
II. In the TP group both urological symptoms and bowel symptoms improved significantly during the testphase (p<0,001), whereas in the FP group only the number of voids and the number of urgency urinary incontinence symptoms significantly improved. Satisfaction scores for US and BS significantly improved in the TP group (p<0,001), whereas only the BS satisfactions score improved in the FP group. TP and FP did not differ significantly in baseline outcomes, neither on diary variables nor on satisfaction scores. 
III. The 24hour fluid intake, 24h diuresis and the adjusted diuresis for fluid intake did not change significantly during the testphase, neither in the TP, nor in the FP group.

The implantation ratios in this trial are similar to previously reported results. (1,2) 
If a more strict definition (only implantation of patients with true success) would have been applied, only 76% would have been implanted. However, this would have implied that a group of patients, a part of the ‘incorrectly implanted cases’ would not have received an implant although showing subjective success and symptom improvement on the other pelvic floor domain than their main problem. This observation advocates for a more holistic approach to the assessment of symptom improvement and to the definition of objective success.  
Using strict criteria for implantation cannot avoid the incidence of false positive cases after SNM on the short term. Therefore it was hypothesized that the immediate decline in subjective success after definitive implantation might be attributable to a certain placebo effect. Since baseline diary values or PROM scores do not differ between FP and TP false positives, a possible false positive case cannot be predicted unless a surrogate variable for the placebo effect exists. Derived from the finding that placebo is amongst others dopamine driven and that dopamine can increase natriuresis (3),  an increased diuresis during the testphase in false positive cases can be expected, presuming that FP are attributable to a placebo effect. This hypothesis however, could not be confirmed from our findings.

SNM has a positive therapeutic effect on both urological symptoms and bowel symptoms in patients with sustained therapeutic subjective success. In the future a more holistic approach should be applied in the baseline history taking and during therapy assessment to optimize care. The number of FP one month after full implant is low but should not be neglected.  The hypothesis that diuresis could be used as a predictor  for false positives, in the light of a potential placebo effect, was not supported. More research for predictive factors notifying the decision-making physician for a potential placebo effect is needed.

Siegel S, Noblett K, Mangel J, Bennett J, Griebling TL, Sutherland SE, et al. Five-Year Followup Results of a Prospective, Multicenter Study of Patients with Overactive Bladder Treated with Sacral Neuromodulation. Journal of Urology. 2018 Jan 1;199(1):229–36.
Widmann B, Galata C, Warschkow R, Beutner U, Ögredici Ö, Hetzer FH, et al. Success and complication rates after sacral neuromodulation for fecal incontinence and constipation: A Single-center Follow-up Study. Journal of Neurogastroenterology and Motility. 2019 Jan 1;25(1):159–70.
Choi MR. Renal dopaminergic system: Pathophysiological implications and clinical perspectives. World Journal of Nephrology. 2015;4(2):196.

Continence 2S2 (2022) 100194
DOI: 10.1016/j.cont.2022.100194