Invasive urodynamic investigations in the management of women with refractory overactive bladder symptoms: FUTURE, a superiority RCT and economic evaluation.

[BACKGROUND] Overactive bladder is a common problem affecting the United Kingdom adult female population. Symptoms include urinary urgency, with or without urgency incontinence, increased daytime urinary frequency and nocturia. Initial conservative treatments for overactive bladder are unsuccessful in 25-40% of women (refractory overactive bladder). Before considering invasive treatments, such as botulinum toxin injection-A or sacral neuromodulation, guidelines recommend urodynamics to confirm diagnosis of detrusor overactivity. However, the clinical and cost effectiveness of urodynamics has never been robustly assessed.

[OBJECTIVES] To compare the clinical and cost effectiveness of urodynamics plus comprehensive clinical assessment versus comprehensive clinical assessment only in the management of refractory overactive bladder in women.

[DESIGN] Parallel-group, multicentre, superiority, open-label, randomised controlled trial. Allocation by remote web-based randomisation (1 : 1 ratio). The cost-effectiveness analysis took the National Health Service perspective with a model-based lifetime time horizon, as informed by a within-trial analysis.

[SETTING] Sixty-three United Kingdom secondary and tertiary hospitals.

[PARTICIPANTS] Women aged ≥ 18 years with refractory overactive bladder or urgency-predominant mixed urinary incontinence who had failed conservative management and pharmacological treatment and were being considered for invasive treatment. Women were excluded if any of the following criteria were met: predominant stress urinary incontinence; previous urodynamics in last 12 months; current pelvic malignancy or clinically significant pelvic mass; bladder pain syndrome; neurogenic bladder; urogenital fistulae; previous treatment with botulinum toxin injection-A or sacral neuromodulation for urinary incontinence; previous pelvic radiotherapy; prolapse beyond introitus; pregnant or planning pregnancy; recurrent urinary tract infection where a significant pathology has not been excluded; and inability to give an informed consent.

[INTERVENTIONS] Urodynamics plus comprehensive clinical assessment (urodynamics arm) versus comprehensive clinical assessment only.

[MAIN OUTCOME MEASURES] Participant-reported success at the last follow-up time point as measured by the Patient Global Impression of Improvement. Primary economic outcome was incremental cost per quality-adjusted life-year gained as modelled over the lifetime of participants.

[RESULTS] A total of 1099 participants were included: 550 randomised to the urodynamics arm and 549 to the comprehensive clinical assessment only arm. At the final follow-up time point, participant-reported success rates of 'very much improved' and 'much improved' were not superior in the urodynamics arm (117 participants; 23.6%) compared to the comprehensive clinical assessment only arm (114 participants; 22.7%) [adjusted odds ratio 1.12 (95% confidence interval 0.73 to 1.74);  = 0.601]. Serious adverse events were low and similar between groups. Based on the estimated incremental costs and quality-adjusted life-years of urodynamics (£463 and 0.011, respectively), the incremental cost-effectiveness ratio was £42,643 per quality-adjusted life-year gained. The cost-effectiveness acceptability curve shows that urodynamics has a 34% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. This probability reduced further when the results were extrapolated over the patient's lifetime. Limitations include: only short-term outcomes were available, and as most participants underwent botulinum toxin injection-A treatment, pre-planned secondary analyses for some outcomes such as sacral neuromodulation were not possible.

[CONCLUSION] Participant-reported success in the urodynamics arm was not superior to the comprehensive clinical assessment only arm at 15-months follow-up. Urodynamics is not cost-effective at a threshold of £20,000 per quality-adjusted life-year gained. Longer-term follow-up is required to explore need for further interventions and treatments and their effect on the clinical and cost-effectiveness analyses.

[TRIAL REGISTRATION] This trial is registered as ISRCTN63268739.

[FUNDING] This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/150/05) and is published in full in Vol. 29, No. 27. See the NIHR Funding and Awards website for further award information.