Subversion of allocation concealment in a randomised controlled trial: a historical case study.

BACKGROUND: If the randomisation process within a trial is subverted, this can lead to selection bias that may invalidate the trial's result. To avoid this problem, it is recommended that some form of concealment should be put into place. Despite ongoing anecdotal concerns about their susceptibility to subversion, a surprising number of trials (over 10%) still use sealed opaque envelopes as the randomisation method of choice. This is likely due in part to the paucity of empirical data quantifying the potential effects of subversion. In this study we report a historical before and after study that compares the use of the sealed envelope method with a more secure centralised telephone allocation approach in order to provide such empirical evidence of the effects of subversion. METHODS: This was an opportunistic before and after study set within a multi-centre surgical trial, which involved 654 patients from 28 clinicians from 23 centres in the UK and Ireland. Two methods of randomly allocating subjects to alternative treatments were adopted: (a) a sealed envelope system administered locally, and (b) a centralised telephone system administered by the trial co-ordination centre. Key prognostic variables were compared between randomisation methods: (a) age at trial entry, a key prognostic factor in the study, and (b) the order in which 'randomisation envelopes' were matched to subjects. RESULTS: The median age of patients allocated to the experimental group with the sealed envelope system, was significantly lower both overall (59 vs 63 years, p < 0.01) and in particular for three clinicians (57 vs 72, p < 0.01; 33 vs 69, p < 0.001; 47 vs 72, p = 0.03). No differences in median age were found between the allocation groups for the centralised system. CONCLUSIONS: Due to inadequate allocation concealment with the sealed envelope system, the randomisation process was corrupted for patients recruited from three clinicians. Centralised randomisation ensures that treatment allocation is not only secure but seen to be secure. Where this proves to be impossible, allocation should at least be performed by an independent third party. Unless it is an absolute requirement, the use of sealed envelopes should be discontinued forthwith.

A multicentre randomised controlled trial comparing elective and selective caesarean section for the delivery of the preterm breech infant.

OBJECTIVE: To determine the optimum mode of delivery for women in preterm breech labour at a gestational age of 26 to 32 weeks. DESIGN: A multicentre randomised controlled trial. SETTING: Twenty-six hospitals in England, UK. PARTICIPANTS: Women with a singleton breech fetus in spontaneous preterm labour between 26 and 32 completed weeks of gestation, with no clear indication for a caesarean section or vaginal breech delivery. INTERVENTION: Random allocation to either 'intention to delivery vaginally' or 'intention to deliver by caesarean section'. MAIN OUTCOME MEASURES: Perinatal mortality, neonatal morbidity, maternal morbidity and gestation at delivery. RESULTS: The trial was closed after 17 months because of low recruitment, by which time substantial numbers of women had been in the eligible gestation period. Thirteen women from six hospitals were recruited. One infant, randomised to and delivered vaginally, was stillborn. Three fetal presentations were cephalic at delivery despite a diagnosis of breech presentation at trial entry. No formal statistical analysis was performed due to the small numbers. CONCLUSIONS: No conclusions about the optimum mode of delivery for women in preterm labour with a fetus presenting by the breech can be drawn from this trial. The low accrual rate was due to clinicians' reluctance to randomise eligible women, reflecting the circumstances and nature of the trial.

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of different knee prostheses: the Knee Arthroplasty Trial (KAT).

BACKGROUND: In the late 1990s, new developments in knee replacement were identified as a priority for research within the NHS. The newer forms of arthroplasty were more expensive and information was needed on their safety and cost-effectiveness. OBJECTIVES: The Knee Arthroplasty Trial examined the clinical effectiveness and cost-effectiveness of four aspects of knee replacement surgery: patellar resurfacing, mobile bearings, all-polyethylene tibial components and unicompartmental replacement. DESIGN: This study comprised a partial factorial, pragmatic, multicentre randomised controlled trial with a trial-based cost-utility analysis which was conducted from the perspective of the NHS and the patients treated. Allocation was computer generated in a 1 : 1 ratio using a central system, stratified by eligible comparisons and surgeon, minimised by participant age, gender and site of disease. Surgeons were not blinded to allocated procedures. Participants were unblinded if they requested to know the prosthesis they received. SETTING: The setting for the trial was UK secondary care. PARTICIPANTS: Patients were eligible for inclusion if a decision had been made for them to have primary knee replacement surgery. Patients were recruited to comparisons for which the surgeon was in equipoise about which type of operation was most suitable. INTERVENTIONS: Patients were randomised to receive a knee replacement with the following: patellar resurfacing or no patellar resurfacing irrespective of the design of the prosthesis used; a mobile bearing between the tibial and femoral components or a bearing fixed to the tibial component; a tibial component made of either only high-density polyethylene ('all polyethylene') or a polyethylene bearing fixed to a metal backing plate with attached stem; or unicompartmental or total knee replacement. MAIN OUTCOME MEASURES: The primary outcome was the Oxford Knee Score (OKS). Other outcomes were Short Form 12; EuroQol 5D; intraoperative and postoperative complications; additional surgery; cost; and cost-effectiveness. Patients were followed up for a median of 10 years; the economic evaluation took a 10-year time horizon, discounting costs and quality-adjusted life-years (QALYs) at 3.5% per annum. RESULTS: A total of 116 surgeons in 34 centres participated and 2352 participants were randomised: 1715 in patellar resurfacing; 539 in mobile bearing; 409 in all-polyethylene tibial component; and 34 in the unicompartmental comparisons. Of those randomised, 345 were randomised to two comparisons. We can be more than 95% confident that patellar resurfacing is cost-effective, despite there being no significant difference in clinical outcomes, because of increased QALYs [0.187; 95% confidence interval (CI) -0.025 to 0.399] and reduced costs (-£104; 95% CI -£630 to £423). We found no definite advantage or disadvantage of mobile bearings in OKS, quality of life, reoperation and revision rates or cost-effectiveness. We found improved functional results for metal-backed tibias: complication, reoperation and revision rates were similar. The metal-backed tibia was cost-effective (particularly in the elderly), costing £35 per QALY gained. CONCLUSIONS: The results provide evidence to support the routine resurfacing of the patella and the use of metal-backed tibial components even in the elderly. Further follow-up is required to assess the stability of these findings over time and to inform the decision between mobile and fixed bearings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45837371. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and the orthopaedic industry. It will be published in full in Health Technology Assessment; Vol. 18, No. 19. See the NIHR Journals Library website for further project information.

Case study: a patient-clinician collaboration that identified and prioritized evidence gaps and stimulated research development.

OBJECTIVE: To assess the effect of a research prioritization partnership that aimed to influence the research agenda relating to urinary incontinence (UI). STUDY DESIGN AND SETTING: Research often neglects important gaps in existing evidence so that decisions must be made about treatments without reliable evidence of their effectiveness. In 2007-2009, a United Kingdom partnership of eight patient and 13 clinician organizations identified and prioritized gaps in the evidence that affect everyday decisions about treatment of UI. The top 10 prioritized research questions were published and reported to research funders in 2009. A year later, new research or funding applications relating to the prioritized topics were identified through reviews of research databases and consultation with funding organizations, elements of the research community, and organizations that participated in the partnership. RESULTS: Since dissemination of the prioritized topics, five studies are known to have been funded, three in development; five new systematic reviews are under way, one is being updated; five questions are under consideration by a national research commissioning body. CONCLUSION: The partnership successfully developed and used a methodology for identification and prioritization of research needs through patient-clinician consensus. Prioritization through consensus can be effective in informing the development of clinically useful research.

Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a major preventable cause of harm for patients in hospital. We aimed to establish whether short-term routine use of antimicrobial catheters reduced risk of CAUTI compared with standard polytetrafluoroethylene (PTFE) catheterisation. METHODS: In our parallel, three group, multicentre, randomised controlled superiority trial, we enrolled adults (aged ≥16 years) requiring short-term (≤14 days) catheterisation at 24 hospitals in the UK. Participants were randomly allocated 1:1:1 with a remote computer allocation to receive a silver alloy-coated catheter, a nitrofural-impregnated catheter, or a PTFE-coated catheter (control group). Patients undergoing unplanned catheterisation were also included and consent for participation was obtained retrospectively. Participants and trial staff were unmasked to treatment assignment. Data were collected by trial staff and by patient-reported questionnaires for 6 weeks after randomisation. The primary outcome was incidence of symptomatic urinary tract infection for which an antibiotic was prescribed by 6 weeks. We postulated that a 3·3% absolute reduction in CAUTI would represent sufficient benefit to recommend routine use of antimicrobial catheters. This study is registered, number ISRCTN75198618. FINDINGS: 708 (10%) of 7102 randomly allocated participants were not catheterised, did not confirm consent, or withdrew, and were not included in the primary analyses. Compared with 271 (12·6%) of 2144 participants in the control group, 263 (12·5%) of 2097 participants allocated a silver alloy catheter had the primary outcome (difference -0·1% [95% CI -2·4 to 2·2]), as did 228 (10·6%) of 2153 participants allocated a nitrofural catheter (-2·1% [-4·2 to 0·1]). Rates of catheter-related discomfort were higher in the nitrofural group than they were in the other groups. INTERPRETATION: Silver alloy-coated catheters were not effective for reduction of incidence of symptomatic CAUTI. The reduction we noted in CAUTI associated with nitrofural-impregnated catheters was less than that regarded as clinically important. Routine use of antimicrobial-impregnated catheters is not supported by this trial. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

A framework for the evaluation of new interventional procedures.

OBJECTIVES: The introduction of new interventional procedures is less regulated than for other health technologies such as pharmaceuticals. Decisions are often taken on evidence of efficacy and short-term safety from small-scale usually observational studies. This reflects the particular challenges of evaluating interventional procedures - the extra facets of skill and training and the difficulty defining a 'new' technology. Currently, there is no framework to evaluate new interventional procedures before they become available in clinical practice as opposed to new pharmaceuticals. This paper proposes a framework to guide the evaluation of a new interventional procedure. PROPOSED FRAMEWORK: A framework was developed consisting of a four-stage progressive evaluation for a new interventional procedure: Stage 1: Development; Stage 2: Efficacy and short-term safety; Stage 3: Effectiveness and cost-effectiveness; and Stage 4: Implementation. The framework also suggests the types of studies or data collection methods that can be used to satisfy each stage. CONCLUSIONS: This paper makes a first step on a framework for generating evidence on new interventional procedures. The difficulties and limitations of applying such a framework are discussed.

Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial).

CONTEXT: Vitamin D or calcium supplementation may have effects on vascular disease and cancer. OBJECTIVE: Our objective was to investigate whether vitamin D or calcium supplementation affects mortality, vascular disease, and cancer in older people. DESIGN AND SETTING: The study included long-term follow-up of participants in a two by two factorial, randomized controlled trial from 21 orthopedic centers in the United Kingdom. PARTICIPANTS: Participants were 5292 people (85% women) aged at least 70 yr with previous low-trauma fracture. INTERVENTIONS: Participants were randomly allocated to daily vitamin D(3) (800 IU), calcium (1000 mg), both, or placebo for 24-62 months, with a follow-up of 3 yr after intervention. MAIN OUTCOME MEASURES: All-cause mortality, vascular disease mortality, cancer mortality, and cancer incidence were evaluated. RESULTS: In intention-to-treat analyses, mortality [hazard ratio (HR) = 0.93; 95% confidence interval (CI) = 0.85-1.02], vascular disease mortality (HR = 0.91; 95% CI = 0.79-1.05), cancer mortality (HR = 0.85; 95% CI = 0.68-1.06), and cancer incidence (HR = 1.07; 95% CI = 0.92-1.25) did not differ significantly between participants allocated vitamin D and those not. All-cause mortality (HR = 1.03; 95% CI = 0.94-1.13), vascular disease mortality (HR = 1.07; 95% CI = 0.92-1.24), cancer mortality (HR = 1.13; 95% CI = 0.91-1.40), and cancer incidence (HR = 1.06; 95% CI = 0.91-1.23) also did not differ significantly between participants allocated calcium and those not. In a post hoc statistical analysis adjusting for compliance, thus with fewer participants, trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated, although all results remain nonsignificant. CONCLUSIONS: Daily vitamin D or calcium supplementation did not affect mortality, vascular disease, cancer mortality, or cancer incidence.

Patellar resurfacing in total knee replacement: five-year clinical and economic results of a large randomized controlled trial.

BACKGROUND: There is conflicting evidence regarding the merits of patellar resurfacing during total knee arthroplasty, as many of the previous randomized controlled trials have not been adequately powered. METHODS: A pragmatic, multicenter, randomized controlled trial was initiated in 1999 in the United Kingdom. Within a partial factorial design, 1715 patients were randomly allocated to receive or not receive patellar resurfacing during total knee arthroplasty. The primary outcome measure was the Oxford Knee Score; secondary measures included the Short Form-12, the EuroQoL 5D, cost, cost-effectiveness, and the need for subsequent knee surgery. RESULTS: The mean Oxford Knee Score was 35 points at five years postoperatively in both groups. There was no significant difference between the groups with respect to the mean Oxford Knee Score (difference, 0.59 point; 95% confidence interval, -0.58 to 1.76 points) or any other outcome measure at five years postoperatively. The outcome was not affected by whether the patella was domed or anatomic. There was no significant difference between the two groups with respect to the prevalence of knee-related readmission, of minor or intermediate reoperation, or of subsequent patella-related surgery. The total health care cost for the primary arthroplasty, subsequent monitoring, and any revision surgery did not differ significantly between the two groups. CONCLUSIONS: In the largest randomized controlled trial of patellar resurfacing reported to date, the functional outcome, reoperation rate, and total health care cost five years after primary total knee arthroplasty were not significantly affected by the addition of patellar resurfacing to the surgical procedure.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

INTRODUCTION: Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. METHODS: This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. RESULTS: A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. CONCLUSIONS: Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. TRIAL REGISTRATION: Prospective Clinical Trials, ISRCTN32188676.

Urinary incontinence in men after formal one-to-one pelvic-floor muscle training following radical prostatectomy or transurethral resection of the prostate (MAPS): two parallel randomised controlled trials.

BACKGROUND: Urinary incontinence is common immediately after prostate surgery. Men are often advised to do pelvic-floor exercises, but evidence to support this is inconclusive. Our aim was to establish if formal one-to-one pelvic floor muscle training reduces incontinence. METHODS: We undertook two randomised trials in men in the UK who were incontinent 6 weeks after radical prostatectomy (trial 1) or transurethral resection of the prostate (TURP; trial 2) to compare four sessions with a therapist over 3 months with standard care and lifestyle advice only. Randomisation was by remote computer allocation. Our primary endpoints, collected via postal questionnaires, were participants' reports of urinary incontinence and incremental cost per quality-adjusted life year (QALY) after 12 months. Group assignment was masked from outcome assessors, but this masking was not possible for participants or caregivers. We used intention-to-treat analyses to compare the primary outcome at 12 months. This study is registered, number ISRCTN87696430. FINDINGS: In the intervention group in trial 1, the rate of urinary incontinence at 12 months (148 [76%] of 196) was not significantly different from the control group (151 [77%] of 195; absolute risk difference [RD] -1·9%, 95% CI -10 to 6). In trial 2, the difference in the rate of urinary incontinence at 12 months (126 [65%] of 194) from the control group was not significant (125 [62%] of 203; RD 3·4%, 95% CI -6 to 13). Adjusting for minimisation factors or doing treatment-received analyses did not change these results in either trial. No adverse effects were reported. In both trials, the intervention resulted in higher mean costs per patient (£180 and £209 respectively) but we did not identify evidence of an economically important difference in QALYs (0·002 [95% CI -0·027 to 0·023] and -0·00003 [-0·026 to 0·026]). INTERPRETATION: In settings where information about pelvic-floor exercise is widely available, one-to-one conservative physical therapy for men who are incontinent after prostate surgery is unlikely to be effective or cost effective. The high rates of persisting incontinence after 12 months suggest a substantial unrecognised and unmet need for management in these men. FUNDING: National Institute of Health Research, Health Technology Assessment (NIHR HTA) Programme.

The introduction of new interventional procedures in the British National Health Service--a qualitative study.

OBJECTIVES: To investigate how interventional procedures (IPs) are introduced into the British National Health Services and identify areas for improvement in the current process. METHODS: Qualitative study using one to one semi-structured interviews. Using the framework approach, the data generated from 14 participants were analysed with coding of emergent themes. Data were analysed separately for providers and commissioner organisations. RESULTS: Variations were observed in how IPs are introduced from both the provider and commissioner perspectives. Patterns of approaches allowed the development of models reflecting practice at each type of organisation: very structured in some places to, unstructured or almost non-existent in others. Factors affecting the decision to introduce a procedure include: immediate costs and benefits, numbers of people affected, training requirements, NICE guidance, nature of procedure, support from colleagues, incentives, public or policy-maker pressure, and aims of the institution. Monitoring was seen as a key area for improvement by many. CONCLUSIONS: These variations indicate that the process of introducing new IPs in the NHS can be improved. Factors affecting decision-making and problems have been identified. The results of our study could inform and help shape future processes of managing and the introduction of new procedures into the NHS.

Reaching a consensus and ranking research priorities in urinary incontinence.

Gaps in the evidence base in healthcare are common, and this is also the case for the management of urinary incontinence. The James Lind Alliance helped patients and clinicians to identify and then prioritise gaps in the evidence base for managing this condition, producing a list of 10 research priorities. This article outlines the process involved in reaching this consensus.

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol.

BACKGROUND: Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. METHODS/DESIGN: A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. DISCUSSION: We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. TRIAL REGISTRATION: Trial registration number - ISRCTN32188676.

Medical versus surgical management for gastro-oesophageal reflux disease (GORD) in adults.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a common condition with up to 20% of patients from Westernised countries experiencing heartburn, reflux or both intermittently. It is unclear whether medical or surgical (laparoscopic fundoplication) management is the most clinically and cost-effective treatment for controlling GORD. OBJECTIVES: To compare the effects of medical management versus laparoscopic fundoplication surgery on health-related and GORD-specific quality of life (QOL) in adults with GORD. SEARCH STRATEGY: We searched CENTRAL (Issue 2, 2009), MEDLINE (1966 to May 2009) and EMBASE (1980 to May 2009). We handsearched conference abstracts and reference lists from published trials to identify further trials. We contacted experts in the field for relevant unpublished material. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing medical management with laparoscopic fundoplication surgery. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from articles identified for inclusion and assessed the methodological quality of eligible trials. Primary outcomes were: health-related and GORD-specific QOL, heartburn, regurgitation and dysphagia. MAIN RESULTS: Four trials were included with a total of 1232 randomised participants. Health-related QOL was reported by four studies although data were combined using fixed-effect models for two studies (Anvari 2006; REFLUX Trial 2008). There were statistically significant improvements in health-related QOL at three months and one year after surgery compared to medical therapy (mean difference (MD) SF36 general health score -5.23, 95% CI -6.83 to -3.62; I(2) = 0%). All four studies reported significant improvements in GORD-specific QOL after surgery compared to medical therapy although data were not combined. There is evidence to suggest that symptoms of heartburn, reflux and bloating are improved after surgery compared to medical therapy, but a small proportion of participants have persistent postoperative dysphagia. Overall rates of postoperative complications were low but surgery is not without risk and postoperative adverse events occurred although they were uncommon. The costs of surgery are considerably higher than the cost of medical management although data are based on the first year of treatment therefore the cost and side effects associated with long-term treatment of chronic GORD need to be considered. AUTHORS' CONCLUSIONS: There is evidence that laparoscopic fundoplication surgery is more effective than medical management for the treatment of GORD at least in the short to medium term. Surgery does carry some risk and whether the benefits of surgery are sustained in the long term remains uncertain. Treatment decisions for GORD should be based on patient and surgeon preference.

Local decision-makers views' of national guidance on interventional procedures in the UK.

OBJECTIVES: To identify how decision-makers in the NHS perceive and manage interventional procedures guidance and to determine whether additional information would be useful. METHODS: Qualitative study using semi-structured interviews with seven providers, six commissioners and one policy-maker. The framework approach was used to analyse transcribed data, and emergent themes coded. Data were analysed separately for providers and commissioner organizations. RESULTS: Perceptions about how guidance is managed in provider organizations varied. Some decision-makers considered that guidance is handled very well whereas others think it is suboptimal and haphazard. It is unclear whether clinicians follow procedure for cautionary guidance. In commissioner organizations, guidance is not seen as a priority by most and is not considered an area that will soon enter routine clinical practice. Moreover, commissioners felt that guidance lacked relevance as there is no consideration of whether procedures are cost-effective or affordable. Despite this, respondents perceived that the content and quality of guidance is satisfactory. Useful additional information for inclusion in guidance would be: prevalence, incidence, cost, patients' views, consequences of using the new intervention, comparative information, effectiveness and cost-effectiveness. CONCLUSIONS: Management of interventional procedures guidance in the NHS can be improved. It is important to understand the ways in which guidance meets and fails to meet decision-makers' needs.

Prioritizing research: Patients, carers, and clinicians working together to identify and prioritize important clinical uncertainties in urinary incontinence.

AIMS: Research often neglects important gaps in existing evidence. Throughout healthcare, clinicians and patients face avoidable "clinical uncertainties" daily, making decisions about treatments without reliable evidence about their effects. This partnership of patients and clinicians aimed to identify and prioritize "clinical uncertainties" relating to treatment of urinary incontinence (UI). METHODS: UK clinician and patient organizations whose remit includes UI were invited to participate. Participating organizations consulted memberships to identify "uncertainties" affecting treatment decisions. "Uncertainties" were also identified in published research recommendations. Prioritization involved two phases: shortlisting of "uncertainties" by organizations; patient-clinician prioritization using established consensus methods. Prioritized "uncertainties" were verified by checking any available relevant up-to-date published systematic reviews. RESULTS: Thirty organizations were invited; 8 patient and 13 clinician organizations participated. Consultation generated 417 perceived "uncertainties," research recommendations 131. Refining, excluding and combining produced a list of 226. Prioritization shortlisted 29 "uncertainties," then a "top ten" (5 submitted by clinicians, 4 by patients, 1 from research recommendations). CONCLUSIONS: The partnership successfully developed and tested a systematic and transparent methodology for patient-clinician consultation and consensus. Through consensus, unanswered research questions of importance to patients and clinicians were identified and prioritized. The final list reflects the heterogeneity of populations, treatments and evidence needs associated with UI. Some prioritized "uncertainties" relate to treatments that are widely used yet whose effects are not thoroughly understood, some to access to care, some to precise surgical questions. Research needs to address the uncertainties range from systematic reviewing to primary research.

Open retropubic colposuspension for urinary incontinence in women.

BACKGROUND: Urinary incontinence is a common and potentially debilitating problem. Open retropubic colposuspension is a surgical treatment which involves lifting the tissues near the bladder neck and proximal urethra in the area behind the anterior pubic bones to correct deficient urethral closure. OBJECTIVES: To assess the effects of open retropubic colposuspension for the treatment of urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Register (searched 30 June 2008) and reference lists of relevant articles. We contacted investigators to locate extra studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in women with symptoms or urodynamic diagnoses of stress or mixed urinary incontinence that included open retropubic colposuspension surgery in at least one trial group. DATA COLLECTION AND ANALYSIS: Studies were evaluated for methodological quality/susceptibility to bias and appropriateness for inclusion and data extracted by two of the reviewers. Trial data were analysed by intervention. Where appropriate, a summary statistic was calculated. MAIN RESULTS: This review included 46 trials involving a total of 4738 women.Overall cure rates were 68.9% to 88.0% for open retropubic colposuspension. Two small studies suggest lower failure rates after open retropubic colposuspension compared with conservative treatment. Similarly, one trial suggests lower failure rates after open retropubic colposuspension compared to anticholinergic treatment. Evidence from six trials showed a lower failure rate for subjective cure after open retropubic colposuspension than after anterior colporrhaphy. Such benefit was maintained over time (RR of failure 0.51; 95% CI 0.34 to 0.76 before the first year, RR 0.43; 95% CI 0.32 to 0.57 at one to five years, RR 0.49; 95% CI 0.32 to 0.75 in periods beyond 5 years). In comparison with needle suspensions there was a lower failure rate after colposuspension in the first year after surgery (RR 0.66; 95% CI 0.42 to 1.03), after the first year (RR 0.48; 95% CI 0.33 to 0.71), and beyond five years (RR 0.32; 95% CI 15 to 0.71). Evidence from twelve trials in comparison with suburethral slings found no significant difference in failure rates in all time periods assessed. Patient-reported failure rates in short, medium and long-term follow-up showed no significant difference between open and laparoscopic retropubic colposuspension, but with wide confidence intervals. In two trials failure was less common after Burch (RR 0.38 95% CI 0.18 to 0.76) than after the Marshall Marchetti Krantz procedure at one to five year follow-up. There were few data at any other follow-up time.In general, the evidence available does not show a higher morbidity or complication rate with open retropubic colposuspension, compared to the other open surgical techniques, although pelvic organ prolapse is more common than after anterior colporrhaphy and sling procedures. AUTHORS' CONCLUSIONS: The evidence available indicates that open retropubic colposuspension is an effective treatment modality for stress urinary incontinence especially in the long term. Within the first year of treatment, the overall continence rate is approximately 85 to 90%. After five years, approximately 70% of patients can expect to be dry. Newer minimal access procedures like tension free vaginal tape look promising in comparison with open colposuspension but their long-term performance is not known and closer monitoring of its adverse event profile must be done. Laparoscopic colposuspension should allow speedier recovery but its relative safety and effectiveness is not known yet.

Evaluation and stages of surgical innovations.

Surgical innovation is an important part of surgical practice. Its assessment is complex because of idiosyncrasies related to surgical practice, but necessary so that introduction and adoption of surgical innovations can derive from evidence-based principles rather than trial and error. A regulatory framework is also desirable to protect patients against the potential harms of any novel procedure. In this first of three Series papers on surgical innovation and evaluation, we propose a five-stage paradigm to describe the development of innovative surgical procedures.

No surgical innovation without evaluation: the IDEAL recommendations.

Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.

Challenges in evaluating surgical innovation.

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures-for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.