Conservative treatment for urinary incontinence in Men After Prostate Surgery (MAPS): two parallel randomised controlled trials.

OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of active conservative treatment, compared with standard management, in regaining urinary continence at 12 months in men with urinary incontinence at 6 weeks after a radical prostatectomy or a transurethral resection of the prostate (TURP). BACKGROUND: Urinary incontinence after radical prostate surgery is common immediately after surgery, although the chance of incontinence is less after TURP than following radical prostatectomy. DESIGN: Two multicentre, UK, parallel randomised controlled trials (RCTs) comparing active conservative treatment [pelvic floor muscle training (PFMT) delivered by a specialist continence physiotherapist or a specialist continence nurse] with standard management in men after radial prostatectomy and TURP. SETTING: Men having prostate surgery were identified in 34 centres across the UK. If they had urinary incontinence, they were invited to enroll in the RCT. PARTICIPANTS: Men with urinary incontinence at 6 weeks after prostate surgery were eligible to be randomised if they consented and were able to comply with the intervention. INTERVENTIONS: Eligible men were randomised to attend four sessions with a therapist over a 3-month period. The therapists provided standardised PFMT and bladder training for male urinary incontinence and erectile dysfunction. The control group continued with standard management. MAIN OUTCOME MEASURES: The primary outcome of clinical effectiveness was urinary incontinence at 12 months after randomisation, and the primary measure of cost-effectiveness was incremental cost per quality-adjusted life-year (QALY). Outcome data were collected by postal questionnaires at 3, 6, 9 and 12 months. RESULTS: Within the radical group (n = 411), 92% of the men in the intervention group attended at least one therapy visit and were more likely than those in the control group to be carrying out any PFMT at 12 months {adjusted risk ratio (RR) 1.30 [95% confidence interval (CI) 1.09 to 1.53]}. The absolute risk difference in urinary incontinence rates at 12 months between the intervention (75.5%) and control (77.4%) groups was -1.9% (95% CI -10% to 6%). NHS costs were higher in the intervention group [£ 181.02 (95% CI £ 107 to £ 255)] but there was no evidence of a difference in societal costs, and QALYs were virtually identical for both groups. Within the TURP group (n = 442), over 85% of men in the intervention group attended at least one therapy visit and were more likely to be carrying out any PFMT at 12 months after randomisation [adjusted RR 3.20 (95% CI 2.37 to 4.32)]. The absolute risk difference in urinary incontinence rates at 12 months between the intervention (64.9%) and control (61.5%) groups for the unadjusted intention-to-treat analysis was 3.4% (95% CI -6% to 13%). NHS costs [£ 209 (95% CI £ 147 to £ 271)] and societal costs [£ 420 (95% CI £ 54 to £ 785)] were statistically significantly higher in the intervention group but QALYs were virtually identical. CONCLUSIONS: The provision of one-to-one conservative physical therapy for men with urinary incontinence after prostate surgery is unlikely to be effective or cost-effective compared with standard care that includes the provision of information about conducting PFMT. Future work should include research into the value of different surgical options in controlling urinary incontinence.

Systematic review and economic modelling of the effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence (SUI) through systematic review and economic modelling. DATA SOURCES: The Cochrane Incontinence Group Specialised Register, electronic databases and the websites of relevant professional organisations and manufacturers, and the following databases: CINAHL, EMBASE, BIOSIS, Science Citation Index and Social Science Citation Index, Current Controlled Trials, ClinicalTrials.gov and the UKCRN Portfolio Database. STUDY SELECTION: The study comprised three distinct elements. (1) A survey of 188 women with SUI to identify outcomes of importance to them (activities of daily living; sex, hygiene and lifestyle issues; emotional health; and the availability of services). (2) A systematic review and meta-analysis of non-surgical treatments for SUI to find out which are most effective by comparing results of trials (direct pairwise comparisons) and by modelling results (mixed-treatment comparisons - MTCs). A total of 88 randomised controlled trials (RCTs) and quasi-RCTs reporting data from 9721 women were identified, considering five generic interventions [pelvic floor muscle training (PFMT), electrical stimulation (ES), vaginal cones (VCs), bladder training (BT) and serotonin-noradrenaline reuptake inhibitor (SNRI) medications], in many variations and combinations. Data were available for 37 interventions and 68 treatment comparisons by direct pairwise assessment. Mixed-treatment comparison models compared 14 interventions, using data from 55 trials (6608 women). (3) Economic modelling, using a Markov model, to find out which combinations of treatments (treatment pathways) are most cost-effective for SUI. DATA EXTRACTION: Titles and abstracts identified were assessed by one reviewer and full-text copies of all potentially relevant reports independently assessed by two reviewers. Any disagreements were resolved by consensus or arbitration by a third person. RESULTS: Direct pairwise comparison and MTC analysis showed that the treatments were more effective than no treatment. Delivering PFMT in a more intense fashion, either through extra sessions or with biofeedback (BF), appeared to be the most effective treatment [PFMT extra sessions vs no treatment (NT) odds ratio (OR) 10.7, 95% credible interval (CrI) 5.03 to 26.2; PFMT + BF vs NT OR 12.3, 95% CrI 5.35 to 32.7]. Only when success was measured in terms of improvement was there evidence that basic PFMT was better than no treatment (PFMT basic vs NT OR 4.47, 95% CrI 2.03 to 11.9). Analysis of cost-effectiveness showed that for cure rates, the strategy using lifestyle changes and PFMT with extra sessions followed by tension-free vaginal tape (TVT) (lifestyle advice-PFMT extra sessions-TVT) had a probability of greater than 70% of being considered cost-effective for all threshold values for willingness to pay for a QALY up to 50,000 pounds. For improvement rates, lifestyle advice-PFMT extra sessions-TVT had a probability of greater than 50% of being considered cost-effective when society's willingness to pay for an additional QALY was more than 10,000 pounds. The results were most sensitive to changes in the long-term performance of PFMT and also in the relative effectiveness of basic PFMT and PFMT with extra sessions. LIMITATIONS: Although a large number of studies were identified, few data were available for most comparisons and long-term data were sparse. Challenges for evidence synthesis were the lack of consensus on the most appropriate method for assessing incontinence and intervention protocols that were complex and varied considerably across studies. CONCLUSIONS: More intensive forms of PFMT appear worthwhile, but further research is required to define an optimal form of more intensive therapy that is feasible and efficient for the NHS to provide, along with further definitive evidence from large, well-designed studies.

The effectiveness and cost-effectiveness of minimal access surgery amongst people with gastro-oesophageal reflux disease - a UK collaborative study. The REFLUX trial.

OBJECTIVES: To evaluate the clinical effectiveness, cost-effectiveness and safety of a policy of relatively early laparoscopic surgery compared with continued medical management amongst people with gastro-oesophageal reflux disease (GORD) judged suitable for both policies. DESIGN: Relative clinical effectiveness was assessed by a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. The economic evaluation compared the cost-effectiveness of the two management policies in order to identify the most efficient provision of future care and describe the resource impact that various policies for fundoplication would have on the NHS. SETTING: A total of 21 hospitals throughout the UK with a local partnership between surgeon(s) and gastroenterologist(s) who shared the secondary care of patients with GORD. PARTICIPANTS: The 810 participants, who were identified retrospectively or prospectively via their participating clinicians, had both documented evidence of GORD (endoscopy and/or manometry/24-hour pH monitoring) and symptoms for longer than 12 months. In addition, the recruiting clinician(s) was clinically uncertain about which management policy was best. INTERVENTION: Of the 810 eligible patients who consented to participate, 357 were recruited to the randomised arm of the trial (178 allocated to surgical management, 179 allocated to continued, but optimised, medical management) and 453 recruited to the parallel non-randomised preference arm (261 chose surgical management, 192 chose to continue with best medical management). The type of fundoplication was left to the discretion of the surgeon. MAIN OUTCOME MEASURES: Participants completed a baseline REFLUX questionnaire, developed specifically for this study, containing a disease-specific outcome measure, the Short Form with 36 Items (SF-36), the EuroQol-5 Dimensions (EQ-5D) and the Beliefs about Medicines and Surgery questionnaires (BMQ/BSQ). Postal questionnaires were completed at participant-specific time intervals after joining the trial (equivalent to approximately 3 and 12 months after surgery). Intraoperative data were recorded by the surgeons and all other in-hospital data were collected by the research nurse. At the end of the study period, participants completed a discrete choice experiment questionnaire. RESULTS: The randomised groups were well balanced at entry. Participants had been taking GORD medication for a median of 32 months; the mean age of participants was 46 years and 66% were men. Of 178 randomised to surgery, 111 (62%) actually had fundoplication. There was a mixture of clinical and personal reasons why some patients did not have surgery, sometimes related to long waiting times. A total or partial wrap procedure was performed depending on surgeon preference. Complications were uncommon and there were no deaths associated with surgery. By the equivalent of 12 months after surgery, 38% in the randomised surgical group (14% amongst those who had surgery) were taking reflux medication compared with 90% in the randomised medical group. There were substantial differences (one-third to one-half standard deviation) favouring the randomised surgical group across the health status measures, the size depending on assumptions about the proportion that actually had fundoplication. These differences were the same or somewhat smaller than differences observed at 3 months. The lower the REFLUX score, the worse the symptoms at trial entry and the larger the benefit observed after surgery. The preference surgical group had the lowest REFLUX scores at baseline. These scores improved substantially after surgery, and by 12 months they were better than those in the preference medical group. The BMQ/BSQ and discrete choice experiment did distinguish the preference groups from each other and from the randomised groups. The latter indicated that the risk of serious complications was the most important single attribute of a treatment option. A within-trial cost-effectiveness analysis suggested that the surgery policy was more costly (mean 2049 pounds) but also more effective [+0.088 quality-adjusted life-years (QALYs)]. The estimated incremental cost per QALY was 19,000-23,000 pounds, with a probability between 46% (when 62% received surgery) and 19% (when all received surgery) of cost-effectiveness at a threshold of 20,000 pounds per QALY. Modelling plausible longer-term scenarios (such as lifetime benefit after surgery) indicated a greater likelihood (74%) of cost-effectiveness at a threshold of 20,000 pounds, but applying a range of alternative scenarios indicated wide uncertainty. The expected value of perfect information was greatest for longer-term quality of life and proportions of surgical patients requiring medication. CONCLUSIONS: Amongst patients requiring long-term medication to control symptoms of GORD, surgical management significantly increases general and reflux-specific health-related quality of life measures, at least up to 12 months after surgery. Complications of surgery were rare. A surgical policy is, however, more costly than continued medical management. At a threshold of 20,000 pounds per QALY it may well be cost-effective, especially when putative longer-term benefits are taken into account, but this is uncertain. The more troublesome the symptoms, the greater the potential benefit from surgery. Uncertainty about cost-effectiveness would be greatly reduced by more reliable information about relative longer-term costs and benefits of surgical and medical policies. This could be through extended follow-up of the REFLUX trial cohorts or of other cohorts of fundoplication patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15517081.

Systematic review of the effectiveness and cost-effectiveness of HealOzone for the treatment of occlusal pit/fissure caries and root caries.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of HealOzone (CurOzone USA Inc., Ontario, Canada) for the management of pit and fissure caries, and root caries. The complete HealOzone procedure involves the direct application of ozone gas to the caries lesion on the tooth surface, the use of a remineralising solution immediately after application of ozone and the supply of a 'patient kit', which consists of toothpaste, oral rinse and oral spray all containing fluoride. DATA SOURCES: Electronic databases up to May 2004 (except Conference Papers Index, which were searched up to May 2002). REVIEW METHODS: A systematic review of the effectiveness of HealOzone for the management of tooth decay was carried out. A systematic review of existing economic evaluations of ozone for dental caries was also planned but no suitable studies were identified. The economic evaluation included in the industry submission was critically appraised and summarised. A Markov model was constructed to explore possible cost-effectiveness aspects of HealOzone in addition to current management of dental caries. RESULTS: Five full-text reports and five studies published as abstracts met the inclusion criteria. The five full-text reports consisted of two randomised controlled trials (RCTs) assessing the use of HealOzone for the management of primary root caries and two doctoral theses of three unpublished randomised trials assessing the use of HealOzone for the management of occlusal caries. Of the abstracts, four assessed the effects of HealOzone for the management of occlusal caries and one the effects of HealOzone for the management of root caries. Overall, the quality of the studies was modest, with many important methodological aspects not reported (e.g. concealment of allocation, blinding procedures, compliance of patients with home treatment). In particular, there were some concerns about the choice of statistical analyses. In most of the full-text studies analyses were undertaken at lesion level, ignoring the clustering of lesions within patients. The nature of the methodological concerns was sufficient to raise doubts about the validity of the included studies' findings. A quantitative synthesis of results was deemed inappropriate. On the whole, there is not enough evidence from published RCTs on which to judge the effectiveness of ozone for the management of both occlusal and root caries. The perspective adopted for the study was that of the NHS and Personal Social Services. The analysis, carried out over a 5-year period, indicated that treatment using current management plus HealOzone cost more than current management alone for non-cavitated pit and fissure caries (40.49 pounds versus 24.78 pounds), but cost less for non-cavitated root caries ( 14.63 pounds versus 21.45 pounds). Given the limitations of the calculations these figures should be regarded as illustrative, not definitive. It was not possible to measure health benefits in terms of quality-adjusted life-years, due to uncertainties around the evidence of clinical effectiveness, and to the fact that the adverse events avoided are transient (e.g. pain from injection of local anaesthetic, fear of the drill). One-way sensitivity analysis was applied to the model. However, owing to the limitations of the economic analysis, this should be regarded as merely speculative. For non-cavitated pit and fissure caries, the HealOzone option was always more expensive than current management when the probability of cure using the HealOzone option was 70% or lower. For non-cavitated root caries the costs of the HealOzone comparator were lower than those of current management only when cure rates from HealOzone were at least 80%. The costs of current management were higher than those of the HealOzone option when the cure rate for current management was 40% or lower. One-way sensitivity analysis was also performed using similar NHS Statement of Dental Remuneration codes to those that are used in the industry submission. This did not alter the results for non-cavitated pit fissure caries as the discounted net present value of current management remained lower than that of the HealOzone comparator ( 22.65 pounds versus 33.39 pounds). CONCLUSIONS: Any treatment that preserves teeth and avoids fillings is welcome. However, the current evidence base for HealOzone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries. To make a decision on whether HealOzone is a cost-effective alternative to current preventive methods for the management of dental caries, further research into its clinical effectiveness is required. Independent RCTs of the effectiveness and cost-effectiveness of HealOzone for the management of occlusal caries and root caries need to be properly conducted with adequate design, outcome measures and methods for statistical analyses.

Systematic review of the clinical effectiveness and cost-effectiveness of tension-free vaginal tape for treatment of urinary stress incontinence.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of tension-free vaginal tape (TVT) in comparison with the standard surgical interventions currently used. DATA SOURCES: Literature searches were carried out on electronic databases and websites for data covering the period 1966--2002. Other sources included references lists of relevant articles; selected experts in the field; abstracts of a limited number of conference proceedings titles; and the Internet. REVIEW METHODS: A systematic review of studies including comparisons of TVT with any of the comparators was conducted. Alternative treatments considered were abdominal retropubic colposuspension (including both open and laparoscopic colposuspension), traditional suburethral sling procedures and injectable agents (periurethral bulking agents). The identified studies were critically appraised and their results summarised. A Markov model comparing TVT with the comparators was developed using the results of the review of effectiveness and data on resource use and costs from previously conducted studies. The Markov model was used to estimate costs and quality-adjusted life-years for up to 10 years following surgery and it incorporated a probabilistic analysis and also sensitivity analysis around key assumptions of the model. RESULTS: Based on limited data from direct comparisons with TVT and from systematic reviews, laparoscopic colposuspension and traditional slings have broadly similar cure rates to TVT and open colposuspension, whereas injectable agents appear to have lower cure rates. TVT is less invasive than colposuspension and traditional sling procedures, and is also usually performed under regional or local anaesthesia. The principal operative complication is bladder perforation. There are currently no randomised controlled trial (RCT) data beyond 2 years post-surgery, and long-term effects are therefore currently not known reliably. TVT was more likely to be considered cost-effective compared with the other surgical procedures. Increasing the absolute probability of cure following TVT reduced the likelihood that TVT would be considered cost-effective. CONCLUSIONS: The long-term performance of TVT in terms of both continence and unanticipated adverse effects is not known reliably at the moment. Despite relatively few robust comparative data, it appears that in the short to medium term TVT's effectiveness approaches that of alternative procedures currently available, and is of lower cost. As TVT is a less invasive procedure, it is possible that some women who would currently be managed non-surgically will be considered eligible for TVT. Increased adoption of TVT will require additional surgeons proficient in the technique. It is likely that some of the higher rates of complications, e.g. bladder perforation, reported for TVT are associated with a 'learning curve'. Appropriate training will therefore be needed for surgeons new to the operation, in respect of both the technical aspects of the procedure and the choice of women suitable for the operation. Further research suggestions include unbiased assessments of longer term performance from follow-up of controlled trials or population-based registries; more data from methodologically sound RCTs using standard outcome measures; a surveillance system to detect longer term complications, if any, associated with the use of tape; and rigorous evaluation before extending the use of TVT to women who are currently managed non-surgically.