4 Research recommendations

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in the full guideline.

4.1 Safety and efficacy of antimuscarinics

What is the safety and efficacy of more recently developed antimuscarinics compared with (a) placebo/usual care and (b) other antimuscarinics in the treatment of neurogenic lower urinary tract dysfunction?

Why this is important

No high-quality clinical trials looking at the use of the newer antimuscarinic drugs in people with neurogenic lower urinary tract dysfunction have been carried out. Both placebo-controlled and comparative studies are lacking. This is important because the more recently developed medications are of unknown efficacy, are more expensive and claim (in the non-neurogenic population) to have fewer adverse effects. The adverse effects of antimuscarinics are mostly due to their action at sites other than the bladder (for example, causing a dry mouth) but there is now increasing concern that antimuscarinic effects on the central nervous system may adversely affect cognitive function in both children with brain damage (caused by cerebral palsy or hydrocephalus) and adults with impaired cognition (caused by cerebral involvement in multiple sclerosis or neurodegenerative diseases).

4.2 Safety and efficacy of botulinum toxin

What is the safety and efficacy of botulinum toxin compared with (a) usual care, (b) antimuscarinics and (c) augmentation cystoplasty in people with neurogenic lower urinary tract dysfunction?

Why this is important

Further research is needed to determine whether repeated intradetrusor injections of botulinum toxin type A have long-term efficacy. The efficacy in terms of continence and upper urinary tract preservation should be studied.

Botulinum toxin injection into the detrusor is an effective means of managing incontinence and improves urodynamic measures of bladder storage with the potential to protect the kidneys from the effects of high intravesical pressures. It is well tolerated in a spectrum of conditions and ages. However, the longer term efficacy over many injections has not been established.

A clinical trial is needed to study the outcome in terms of continence and renal preservation over many cycles of repeated injection. Quality of life is an important outcome. A trial should enrol children and adults. The indications for botulinum toxin need not be modified for inclusion, but entrants into a trial must have anatomically normal kidneys (on imaging) and normal renal function.

What is the safety and efficacy of botulinum toxin compared with (a) usual care, (b) antimuscarinics and (c) augmentation cystoplasty in people with primary cerebral conditions with lower urinary tract dysfunction?

Why this is important

The effects of intradetrusor botulinum toxin type A injection should be investigated in groups of people with underlying cerebral conditions that are associated with lower urinary tract dysfunction, as well as those with spinal cord injury, spina bifida and multiple sclerosis. Reports of its use in other conditions are limited to small numbers of patients within case series studies that include heterogeneous groups of patients. Potential benefits of successful treatment in cerebral disease may include the avoidance of cognitive impairment, which can be seen as a side effect of antimuscarinic medication.

A trial should include people with primary cerebral conditions including (but not restricted to) stroke, head injury and cerebral palsy, but excluding multiple sclerosis. Children and adults should be recruited. Tolerability and acceptability are important outcomes, as well as the primary outcomes of continence, preservation of the upper urinary tracts and quality of life. Measurement of carer burden and quality of life is also important.

4.3 Management strategies to reduce the risk of symptomatic urinary tract infections

In people with neurogenic lower urinary tract dysfunction, which management strategies (including the use of prophylactic antibiotics and various invasive and non-invasive techniques to aid bladder drainage) reduce the risk of symptomatic urinary tract infections?

Why this is important

Recurrent urinary tract infections in people with neurogenic bladder dysfunction are a cause of considerable morbidity. Urinary tract infections may exacerbate incontinence, cause symptoms of malaise and may progress to involve the upper urinary tract with possible loss of renal function. In the population with neurological diseases such as multiple sclerosis, Parkinson's disease and dementia, the rise in temperature with urinary tract infections can cause deterioration in neurological function and even a relapse of multiple sclerosis. There are therefore numerous reasons why people with neurogenic lower urinary tract dysfunction should avoid urinary tract infections.

The causes for the high prevalence of urinary tract infections in such people include loss of physiological bladder function and high intravesical pressures. Intermittent or permanent catheterisation inevitably exacerbate the problem, but incomplete bladder emptying is also a predisposing factor for urinary tract infections.

Research in this area is faced with methodological difficulties, not least because it may be difficult to distinguish between bladder colonisation (asymptomatic bacteriuria) and true infection.

In view of the considerable clinical burden of urinary tract infections and the global problem of antibiotic resistance, it is important to establish whether or not any infection prevention strategies, including patient training or the provision of information relating to prophylactic antibiotics are effective in reducing symptomatic urinary tract infections.

4.4 Bladder management strategies

What are the long-term risks and effects on quality of life of different bladder management strategies for lower urinary tract dysfunction in people with neurological disease?

Why this is important

The range of bladder management strategies available to manage lower urinary tract dysfunction in neurological disease includes permanent urethral catheterisation and suprapubic catheterisation, intermittent self-catheterisation, penile sheath collection systems and pads. However, there is very sparse evidence about which strategies are most acceptable to patients and/or their family members and carers. The current research base relates mainly to the spinal injury population but may be relevant to people with other neurological diseases.

Bladder management strategies are a long-term treatment with implications for maintaining health and quality of life. In order to make informed choices about the most appropriate method of bladder management, patients and/or their family members and carers require information about the risks and benefits of the available options. There is currently little evidence about which methods are most likely to produce long-term complications (renal impairment, urinary stones and infections, hydronephrosis, bladder malignancy). The effect on quality of life for patients and/or their family members and carers of different bladder management strategies is not known. There are methodological difficulties due to the heterogeneity of the population with neurological disease, the long time course of treatments and the presence of cognitive impairment in some sub-populations.

Proposed studies could include prospective cohort studies of disease-specific populations examining the effect of each method on quality of life using both generic and disease-specific assessment methods. In addition, prospective screening for complications including renal impairment, stone formation and infection should be carried out and comparisons made for each bladder management method. Particular emphasis should be placed on quality-of-life outcomes for family members and carers, especially for those looking after people with cognitive impairment.

  • National Institute for Health and Care Excellence (NICE)