DEEP Study: Modeling Outcomes and Costs of Persistent Orofacial Pain.

KNOWLEDGE OF TRANSFER STATEMENT: Despite a substantial number of consultations, individuals experiencing the care pathways in this study continued to have far from perfect health over their life course. The modeling suggests they would only experience 18 y in "perfect health." There is considerable scope to improve current care/outcomes and patient experience.

Incorporating ex-vivo lung perfusion into the UK adult lung transplant service: an economic evaluation and decision analytic model.

BACKGROUND: An estimated 20-30% of end-stage lung disease patients awaiting lung transplant die whilst on the waiting list due to a shortage of suitable donor lungs. Ex-Vivo Lung Perfusion is a technique that reconditions donor lungs initially not deemed usable in order to make them suitable for transplantation, thereby increasing the donor pool. In this study, an economic evaluation was conducted as part of DEVELOP-UK, a multi-centre study assessing the clinical and cost-effectiveness of the Ex-Vivo Lung Perfusion technique in the United Kingdom. METHODS: We estimated the cost-effectiveness of a UK adult lung transplant service combining both standard and Ex-Vivo Lung Perfusion transplants compared to a service including only standard lung transplants. A Markov model was developed and populated with a combination of DEVELOP-UK, published and clinical routine data, and extrapolated to a lifetime horizon. Probabilistic sensitivity and scenario analyses were used to explore uncertainty in the final outcomes. RESULTS: Base-case model results estimated life years gained of 0.040, quality-adjusted life-years (QALYs) gained of 0.045 and an incremental cost per QALY of £90,000 for Ex-Vivo Lung Perfusion. Scenario analyses carried out suggest that an improved rate of converting unusable donor lungs using Ex-Vivo Lung Perfusion, similar resource use post-transplant for both standard and EVLP lung transplant and applying increased waiting list costs would reduce ICERs to approximately £30,000 or below. CONCLUSION: DEVELOP-UK base-case results suggest that incorporating Ex-Vivo Lung Perfusion into the UK adult lung transplant service is more effective, increasing the number of donor lungs available for transplant, but would not currently be considered cost-effective in the UK using the present NICE threshold. However, results were sensitive to change in some model parameters and in several plausible scenario analyses results indicate that a service incorporating Ex-vivo lung perfusion would be considered cost-effective . TRIAL REGISTRATION: ISRCTN registry number: ISRCTN44922411 . Date of registration: 06/02/2012. Retrospectively registered.

DEEP Study: Indirect and Out-of-pocket Costs of Persistent Orofacial Pain.

Persistent orofacial pain (POFP) is common and caused by a group of conditions affecting the face, head, or mouth. Recent research highlighted a problematic care pathway with high costs to the health care provider, but the financial impact on patients and employers is not understood. This study aimed to describe patient (out-of-pocket) and employer (indirect) costs of POFP and to identify whether the dichotomized Graded Chronic Pain Scale (GCPS) was predictive of costs. A cohort of 198 patients was recruited from primary and secondary care settings in North East England and followed over a 24-mo period. Patients completed the GCPS and Use of Services and Productivity Questionnaire every 6 mo and a Time and Travel Questionnaire at 14 mo. Questionnaires examined the implications of health care utilization on patients' everyday lives and personal finances. Time and travel costs were calculated and applied to use-of-services data to estimate out-of-pocket costs, while the human capital method and QQ method (quantity and quality of work completed) were used to estimate absenteeism and presenteeism costs, respectively. Per person per 6-mo period (in 2017 pounds sterling), mean out-of-pocket costs were £333 (95% CI, £289 to £377), and indirect costs were £1,242 (95% CI, £1,014 to £1,470). Regression analyses indicated that over 6 mo, the GCPS was predictive of the following: out-of-pocket costs-a difference of £311 between low and high GCPS per person per 6-mo period (95% CI, £280 to £342; P < 0.01, n = 705 observations over 24 mo); indirect costs-a difference of £2,312 between low and high GCPS per person per 6-mo period (95% CI, £1,886 to £2,737; P < 0.01; n = 352 observations over 24 mo). This analysis highlights "hidden" costs of POFP and supports the use of the dichotomized GCPS to identify patients at risk of higher impact and associated costs and thereby stratify care pathways and occupational health support appropriately.

Cost implications for the NHS of using the Alere™ i Influenza A & B near patient test with nasal swabs.

BACKGROUND: Influenza is an acute viral infection of the respiratory tract. A rapid confirmatory diagnosis of influenza is important, since it is highly transmissible and outbreaks of influenza within the hospital setting increase morbidity and mortality. The objective of this study was to evaluate the cost implications, from the perspective of the UK NHS, of using on-label nasal swabs with the Alere™ i Influenza A & B test in a near patient setting. METHODS: A cost consequence model was developed. The time horizon of the model was from hospital admission on suspicion of influenza until the end of treatment (following a diagnosis of influenza or discharge from hospital). Data on the prevalence of influenza and the sensitivity and specificity of the Alere™ i Influenza A & B test came from two prospective observational diagnostic accuracy studies. Costs were obtained from published resources. Uncertainties in the model data were investigated using deterministic, one-way sensitivity analyses. RESULTS: Using the Alere™ i Influenza A & B point of care test with nasal swabs (on label) in NHS medical assessment units and emergency departments could save approximately £242,730 per 1000 adults presenting with influenza-like symptoms. The main cause for this was reduced times to availability of the result compared with the laboratory RT-PCR test. Other key drivers of savings were the cost of isolation, the prevalence of influenza, the specificity of the test, and the availability of isolation resources. CONCLUSIONS: The Alere™ i Influenza A & B point of care test would have greatest impact in hospitals that have extensive delays in the time to receive a result. Sensitivity analyses identified the model parameters which would have greatest effect on the result and confirmed that assumptions were conservative, i.e. did not change key results.

Diagnostic accuracy and cost analysis of the Alere™ i Influenza A&B near-patient test using throat swabs.

BACKGROUND: Clinical diagnostic sensitivity alone is inadequate in the diagnosis of influenza. Polymerase chain reaction (PCR) testing is sensitive but the inherent delays in result availability potentially prolong time to isolation and treatment. Until recently no near-patient test (NPT) has demonstrated adequate sensitivity for routine clinical use. AIM: To evaluate diagnostic accuracy, time to result availability, clinical impact, and cost consequences of Alere™ i Influenza A&B NPT (Alere Inc., Waltham, MA, USA) using off-label throat swabs. METHODS: Prospective, multi-centre [four UK National Health Service (NHS) hospitals], diagnostic accuracy cohort study with cost modelling. Throat swab samples from suspected influenza patients were tested for influenza using the reference standard of PCR; a second throat swab was tested using NPT. FINDINGS: A total of 827 participants were recruited; 589 were suitable for analysis: sensitivity was 75.8% [95% confidence interval (CI): 67.0-84.6]; specificity was 96.8% (95% CI: 95.2-98.3). Sensitivity varied between Sheffield (Northern General Hospital: 82.1%; Royal Hallamshire Hospital: 83.3%) and other sites (Doncaster Royal Infirmary: 71.4%; Newcastle's Royal Victoria Infirmary: 50.0%) whereas specificity was high (92-100%). Positive predictive value (PPV) was 81.2% (95% CI: 72.9-89.5) with negative predictive value 95.6% (95% CI: 93.9-97.4) with observed prevalence of 15.4%. Median time to result for PCR was 1.1 days (on-site laboratories) and 5.2 days (remote laboratories). Isolation findings: 75% influenza positive not isolated; 69% of isolated participants did not have influenza. For a cohort of 1000 participants, annual estimated non-diagnostic cost savings with NPT are £215,040. CONCLUSION: This first prospective study of the Alere i NPT using throat swabs demonstrates high specificity, high PPV during seasonal epidemics, and rapid result availability which could lead to substantial cost savings.

'Thinking that somebody's going to delay [a tonsillectomy] for one to two years is quite horrifying really': a qualitative feasibility study for the NAtional Trial of Tonsillectomy IN Adults (NATTINA Part 2).

OBJECTIVES: Level one evidence on the value of adult tonsillectomy versus non-surgical management remains scarce. Before embarking on a costly national randomised controlled trial, it is essential to establish its feasibility. DESIGN: Feasibility study with in-depth qualitative and cognitive interviews. SETTING: ENT staff and patients were recruited from nine hospital centres across England and Scotland. PARTICIPANTS: Patients who were referred for tonsillectomy (n = 15), a convenience sample of general practitioners (n = 11) and ear, nose and throat staff (n = 22). MAIN OUTCOME MEASURES: To ascertain whether ear, nose and throat staff would be willing to randomise patients to the treatment arms. To assess general practitioners' willingness to refer patients to the NAtional Trial of Tonsillectomy IN Adults (NATTINA) centres. To assess patients' willingness to be randomised and the acceptability of the deferred surgery treatment arm. To ascertain whether the study could progress to the pilot trial stage. RESULTS: Ear, nose and throat staff and general practitioners were willing to randomise patients to the proposed NATTINA. Not all ENT staff were in equipoise concerning the treatment pathways. Patients were reluctant to be randomised into the deferred surgery group if they had already waited a substantial time before being referred. CONCLUSIONS: Findings suggest that the NATTINA may not be feasible. Proposed methods could not be realistically assessed without a pilot trial. Due to the importance of the question, as evidenced by NATTINA clinicians, and strong support from ENT staff, the pilot trial proceeded, with modifications.

Healthcare Cost and Impact of Persistent Orofacial Pain: The DEEP Study Cohort.

Few data are available on the healthcare costs of those suffering from persistent orofacial pain (POFP). This cohort and cost analysis study examined the direct costs of POFP from the perspective of the healthcare provider (specifically, the UK National Health Service) in 2012 pounds sterling and sought to identify whether dichotomized (high, IIb to IV; low, 0 to IIa) graded chronic pain scale (GCPS) status is predictive of the total cost of healthcare over the last 6 mo. The healthcare utilization data of 198 patients with POFP were collected using a structured interview and a validated "use of services and productivity" questionnaire. Unit costs were used with these utilization data to calculate direct healthcare costs in 3 categories: consultation, medication, and appliances and interventions. Consultation costs were a significant proportion of cumulative healthcare cost (P < 0.001). Dichotomized GCPS status was predictive of increased healthcare cost over the last 6 mo, accounting for an average increase of £366 (95% confidence interval, 135 to 598; P < 0.01) when moving from a low GCPS status to a high GCPS status. Given the predictive capability of dichotomized GCPS status and the success of stratified models of care for other persistent pain conditions, dichotomized GCPS status may offer an opportunity to help determine stratification of care for patients with POFP.

Monitoring ocular hypertension, how much and how often? A cost-effectiveness perspective.

OBJECTIVE: To assess the efficiency of alternative monitoring services for people with ocular hypertension (OHT), a glaucoma risk factor. DESIGN: Discrete event simulation model comparing five alternative care pathways: treatment at OHT diagnosis with minimal monitoring; biennial monitoring (primary and secondary care) with treatment if baseline predicted 5-year glaucoma risk is ≥6%; monitoring and treatment aligned to National Institute for Health and Care Excellence (NICE) glaucoma guidance (conservative and intensive). SETTING: UK health services perspective. PARTICIPANTS: Simulated cohort of 10 000 adults with OHT (mean intraocular pressure (IOP) 24.9 mm Hg (SD 2.4). MAIN OUTCOME MEASURES: Costs, glaucoma detected, quality-adjusted life years (QALYs). RESULTS: Treating at diagnosis was the least costly and least effective in avoiding glaucoma and progression. Intensive monitoring following NICE guidance was the most costly and effective. However, considering a wider cost-utility perspective, biennial monitoring was less costly and provided more QALYs than NICE pathways, but was unlikely to be cost-effective compared with treating at diagnosis (£86 717 per additional QALY gained). The findings were robust to risk thresholds for initiating monitoring but were sensitive to treatment threshold, National Health Service costs and treatment adherence. CONCLUSIONS: For confirmed OHT, glaucoma monitoring more frequently than every 2 years is unlikely to be efficient. Primary treatment and minimal monitoring (assessing treatment responsiveness (IOP)) could be considered; however, further data to refine glaucoma risk prediction models and value patient preferences for treatment are needed. Consideration to innovative and affordable service redesign focused on treatment responsiveness rather than more glaucoma testing is recommended.

Economic evaluation of nurse-led intensive care follow-up programmes compared with standard care: the PRaCTICaL trial.

OBJECTIVE: Following intensive care discharge, many patients suffer severe physical and psychological morbidity and a continuing high use of health services. Follow-up programmes have been proposed to improve the outcomes for these patients. We tested the hypothesis that nurse-led intensive care follow-up programmes are cost-effective. METHODS: A pragmatic, multicentre, randomised controlled trial of nurse-led intensive care unit follow-up programmes versus standard care. A cost-utility analysis was conducted after 12 months' follow-up to compare the two interventions. Costs were assessed from the perspective of the UK NHS and outcomes were measured in quality-adjusted life years (QALYs) based upon responses to the EQ-5D administered at baseline, 6 and 12 months. RESULTS: A total of 286 patients were recruited to the trial. Total mean cost was £ 5,789 for standard care and £ 7,577 for the discharge clinic. The adjusted difference in means was £ 2,435 [95 % confidence interval (CI) -297 to 5,566]. Mean QALYs were 0.58 for standard care and 0.60 for the discharge clinic. The adjusted mean difference was -0.003 (95 % CI -0.066 to 0.060). If society were willing to pay £ 20,000 per QALY then there would be a 93 % chance that standard care would be considered most efficient. CONCLUSIONS: A nurse-led intensive care unit (ICU) follow-up programme showed no evidence of being cost-effective at 12 months. Further work should focus on evidence-based development of discharge clinic services and current ICU follow-up programmes should review their practice in light of these results.

Types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial- and antiseptic-impregnated urethral catheters (the CATHETER trial).

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a major preventable cause of harm for patients in hospital and incurs significant costs for health-care providers such as the UK NHS. Many preventative strategies and measures have been introduced to minimise CAUTI risk, including the use of antimicrobial catheters. However, there is considerable uncertainty regarding their usefulness in terms of reducing symptomatic CAUTI, and whether or not they are cost-effective. OBJECTIVES: Do antimicrobial catheters reduce the rate of symptomatic urinary tract infection (UTI) during short-term hospital use and is their use cost-effective for the UK NHS? DESIGN: A pragmatic multicentre UK randomised controlled trial comparing three catheters as they would be used in the UK NHS: antimicrobial-impregnated (nitrofurazone) and antiseptic-coated (silver alloy) catheters with the standard polytetrafluoroethylene (PTFE)-coated catheters. Economic evaluation used a decision model populated with data from the trial. Sensitivity analysis was used to explore uncertainty. SETTING: Relevant clinical departments in 24 NHS hospitals throughout the UK. PARTICIPANTS: Adults requiring temporary urethral catheterisation for a period of between 1 and 14 days as part of their care, predominantly as a result of elective surgery. INTERVENTIONS: Eligible participants were randomised 1 : 1 : 1 to one of three types of urethral catheter in order to make the following pragmatic comparisons: nitrofurazone-impregnated silicone catheter compared with standard PTFE-coated latex catheter; and silver alloy-coated hydrogel latex catheter compared with standard PTFE-coated latex catheter. MAIN OUTCOME MEASURES: The primary outcome for clinical effectiveness was the incidence of UTI at any time up to 6 weeks post randomisation. This was defined as any symptom reported during catheterisation, up to 3 days or 1 or 2 weeks post catheter removal or 6 weeks post randomisation combined with a prescription of antibiotics, at any of these times, for presumed symptomatic UTI. The primary economic outcome was incremental cost per quality-adjusted life-year (QALY). Health-care costs were estimated from NHS sources with QALYs calculated from participant completion of the European Quality of Life-5 Dimensions (EQ-5D). RESULTS: Outcome analyses encompassed 6394 (90%) of 7102 participants randomised. The rate of symptomatic UTI within 6 weeks of randomisation was 10.6% in the nitrofurazone group (n = 2153; -2.1% absolute risk difference), 12.5% in the silver alloy group (n = 2097; -0.1% absolute risk difference) and 12.6% in the PTFE group (n = 2144). The effect size {odds ratio (OR) [97.5% confidence interval (CI)]} was 0.82 (97.5% CI 0.66 to 1.01) for nitrofurazone (p = 0.037) and 0.99 (97.5% CI 0.81 to 1.22) for silver alloy (p = 0.92) catheters. The nitrofurazone catheters were more likely to cause discomfort during use and on removal. The primary economic analysis suggested that nitrofurazone-impregnated catheters would be, on average, the least costly (> £7 less than PTFE) and most effective option at current NHS prices. There was a 73% chance that nitrofurazone would be cost saving and an 84% chance that the incremental cost per QALY would be < £30,000. At the trial price (£6.46), silver alloy catheters were very unlikely to be cost-effective. These results were unchanged in sensitivity analyses, although when the length of stay cost was excluded the incremental cost per QALY for nitrofurazone against PTFE was £28,602. CONCLUSIONS: The trial estimate of clinical effectiveness for nitrofurazone-impregnated catheters was less than the pre-specified minimum absolute risk difference that we considered important (-3.3%), and the surrounding CI included zero, indicating that any reduction in catheter-associated UTI was uncertain. Economic analysis, although associated with uncertainty, suggested that nitrofurazone-impregnated catheters may be cost-effective for the NHS. The trial ruled out the possibility that silver alloy-coated catheters might reach the pre-set degree of clinical effectiveness and that their use was unlikely to be cost-effective. These findings should be considered by patients, clinicians and health-care policy-makers to determine whether or not a change in practice is worthwhile. Future research should be aimed at determining the minimum clinically important difference in terms of CAUTI prevention in comparative trials, and to identify reliable methods which can detect the impact of the intervention on quality of life and other drivers of cost, when the intervention is a subsidiary part of overall treatment plans.

Systematic review and economic modelling of the relative clinical benefit and cost-effectiveness of laparoscopic surgery and robotic surgery for removal of the prostate in men with localised prostate cancer.

BACKGROUND: Complete surgical removal of the prostate, radical prostatectomy, is the most frequently used treatment option for men with localised prostate cancer. The use of laparoscopic (keyhole) and robot-assisted surgery has improved operative safety but the comparative effectiveness and cost-effectiveness of these options remains uncertain. OBJECTIVE: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of robotic radical prostatectomy compared with laparoscopic radical prostatectomy in the treatment of localised prostate cancer within the UK NHS. DATA SOURCES: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, BIOSIS, Science Citation Index and Cochrane Central Register of Controlled Trials were searched from January 1995 until October 2010 for primary studies. Conference abstracts from meetings of the European, American and British Urological Associations were also searched. Costs were obtained from NHS sources and the manufacturer of the robotic system. Economic model parameters and distributions not obtained in the systematic review were derived from other literature sources and an advisory expert panel. REVIEW METHODS: Evidence was considered from randomised controlled trials (RCTs) and non-randomised comparative studies of men with clinically localised prostate cancer (cT1 or cT2); outcome measures included adverse events, cancer related, functional, patient driven and descriptors of care. Two reviewers abstracted data and assessed the risk of bias of the included studies. For meta-analyses, a Bayesian indirect mixed-treatment comparison was used. Cost-effectiveness was assessed using a discrete-event simulation model. RESULTS: The searches identified 2722 potentially relevant titles and abstracts, from which 914 reports were selected for full-text eligibility screening. Of these, data were included from 19,064 patients across one RCT and 57 non-randomised comparative studies, with very few studies considered at low risk of bias. The results of this study, although associated with some uncertainty, demonstrated that the outcomes were generally better for robotic than for laparoscopic surgery for major adverse events such as blood transfusion and organ injury rates and for rate of failure to remove the cancer (positive margin) (odds ratio 0.69; 95% credible interval 0.51 to 0.96; probability outcome favours robotic prostatectomy = 0.987). The predicted probability of a positive margin was 17.6% following robotic prostatectomy compared with 23.6% for laparoscopic prostatectomy. Restriction of the meta-analysis to studies at low risk of bias did not change the direction of effect but did decrease the precision of the effect size. There was no evidence of differences in cancer-related, patient-driven or dysfunction outcomes. The results of the economic evaluation suggested that when the difference in positive margins is equivalent to the estimates in the meta-analysis of all included studies, robotic radical prostatectomy was on average associated with an incremental cost per quality-adjusted life-year that is less than threshold values typically adopted by the NHS (£30,000) and becomes further reduced when the surgical capacity is high. LIMITATIONS: The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. CONCLUSIONS: This study demonstrated that robotic prostatectomy had lower perioperative morbidity and a reduced risk of a positive surgical margin compared with laparoscopic prostatectomy although there was considerable uncertainty. Robotic prostatectomy will always be more costly to the NHS because of the fixed capital and maintenance charges for the robotic system. Our modelling showed that this excess cost can be reduced if capital costs of equipment are minimised and by maintaining a high case volume for each robotic system of at least 100-150 procedures per year. This finding was primarily driven by a difference in positive margin rate. There is a need for further research to establish how positive margin rates impact on long-term outcomes. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Surveillance for ocular hypertension: an evidence synthesis and economic evaluation.

OBJECTIVES: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways. DESIGN: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model. SETTING: Primary and secondary care. PARTICIPANTS: Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences). INTERVENTIONS: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community. MAIN OUTCOME MEASURES: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs). RESULTS: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence. LIMITATIONS: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates. CONCLUSIONS: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment. FUNDING: The National Institute for Health Research Health Technology Assessment Programme.

The clinical effectiveness and cost-effectiveness of different surveillance mammography regimens after the treatment for primary breast cancer: systematic reviews registry database analyses and economic evaluation.

BACKGROUND: Following primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear. OBJECTIVES: To identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens. METHODS: A survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost-utility of differing surveillance regimens. RESULTS: The majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring >20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was <10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted life-year of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727. LIMITATIONS: Few studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model. CONCLUSIONS: Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

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.

Clinical effectiveness and cost-effectiveness of imatinib dose escalation for the treatment of unresectable and/or metastatic gastrointestinal stromal tumours that have progressed on treatment at a dose of 400 mg/day: a systematic review and economic evaluation.

BACKGROUND: Imatinib dose escalation is advocated for gastrointestinal stromal tumour (GIST) treatment, but its effectiveness compared with sunitinib and best supportive care (BSC) after failure at the 400 mg/day dose is unknown. OBJECTIVES: To assess the effectiveness and cost-effectiveness of imatinib at escalated doses of 600 or 800 mg/day for patients with unresectable and/or metastatic GISTs whose disease had progressed on 400 mg/day. DATA SOURCES: Electronic databases, including MEDLlNE, MEDLINE In-Process, EMBASE, BIOSIS, Science Citation Index, Health Management Information Consortium and the Cochrane Controlled Trials Register, were searched until September 2009. REVIEW METHODS: A systematic review of the literature was carried out according to standard methods. An economic model was constructed to assess the cost-effectiveness of seven alternative pathways for treating patients with unresectable and/or metastatic GISTs. RESULTS: Five primary studies involving 669 people were included for clinical effectiveness; four reported imatinib and one reported sunitinib. The data were essentially observational as none of the studies was designed to specifically assess treatment of patients whose disease had progressed on 400 mg/day imatinib. For 600 mg/day imatinib, between 26% and 42% of patients showed either a partial response (PR) or stable disease (SD). Median time to progression was 1.7 months (range 0.7-24.9 months). For 800 mg/day imatinib, between 29% and 33% of patients showed either a PR or SD. Median overall survival (OS) was 19 months [95% confidence interval (CI) 13 to 23 months]. Progression-free survival ranged from 81 days to 5 months (95% CI 2 to 10 months). Median duration of response was 153 days (range 37-574 days). Treatment progression led to 88% discontinuations but between 16% and 31% of patients required a dose reduction, and 23% required a dose delay. There was a statistically significant increase in the severity of fatigue (p < 0.001) and anaemia (p = 0.015) following dose escalation. For sunitinib, median OS was 90 weeks (95% CI 73 to 106 weeks). For the cost-effectiveness review, only one full-text study and one abstract were identified, comparing imatinib at an escalated dose, sunitinib and BSC, although neither was based on a UK context. The definition of BSC was not consistent across the studies, and the pattern of resources (including drugs for treatment) and measures of effectiveness also varied. Within the model, BSC (assumed to include continuing medication to prevent tumour flare) was the least costly and least effective. It would be the care pathway most likely to be cost-effective when the cost per quality-adjusted life-year threshold was < £25,000. Imatinib at 600 mg/day was most likely to be cost-effective at a threshold between £25,000 and £45,000. Imatinib at 600 mg/day followed by further escalation followed by sunitinib was most likely to be cost-effective at a threshold > £45,000. LIMITATIONS: The evidence base was sparse, data were non-randomised and potentially biased. The economic model results are surrounded by a considerable degree of uncertainty and open to biases of unknown magnitude and direction. CONCLUSIONS: Around one-third of patients with unresectable and/or metastatic GIST, who fail on 400 mg/day of imatinib, may show response or SD with escalated doses. Between a threshold of £25,000 and £45,000, provision of an escalated dose of imatinib would be most likely to be cost-effective. However, these results should be interpreted with caution owing to the limited evidence available on outcomes following imatinib dose escalation or sunitinib for this group of patients. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

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.

Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer.

OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis (PDD) compared with white light cystoscopy (WLC), and urine biomarkers [fluorescence in situ hybridisation (FISH), ImmunoCyt, NMP22] and cytology for the detection and follow-up of bladder cancer. DATA SOURCES: Major electronic databases including MEDLINE, MEDLINE In-Process, EMBASE, BIOSIS, Science Citation Index, Health Management Information Consortium and the Cochrane Controlled Trials Register were searched until April 2008. REVIEW METHODS: A systematic review of the literature was carried out according to standard methods. An economic model was constructed to assess the cost-effectiveness of alternative diagnostic and follow-up strategies for the diagnosis and management of patients with bladder cancer. RESULTS: In total, 27 studies reported PDD test performance. In pooled estimates [95% confidence interval (CI)] for patient-level analysis, PDD had higher sensitivity than WLC [92% (80% to 100%) versus 71% (49% to 93%)] but lower specificity [57% (36% to 79%) versus 72% (47% to 96%)]. Similar results were found for biopsy-level analysis. The median sensitivities (range) of PDD and WLC for detecting lower risk, less aggressive tumours were similar for patient-level detection [92% (20% to 95%) versus 95% (8% to 100%)], but sensitivity was higher for PDD than for WLC for biopsy-level detection [96% (88% to 100%) versus 88% (74% to 100%)]. For more aggressive, higher-risk tumours the median sensitivity of PDD for both patient-level [89% (6% to 100%)] and biopsy-level [99% (54% to 100%)] detection was higher than those of WLC [56% (0% to 100%) and 67% (0% to 100%) respectively]. Four RCTs comparing PDD with WLC reported effectiveness outcomes. PDD use at transurethral resection of bladder tumour resulted in fewer residual tumours at check cystoscopy [relative risk, RR, 0.37 (95% CI 0.20 to 0.69)] and longer recurrence-free survival [RR 1.37 (95% CI 1.18 to 1.59)] compared with WLC. In 71 studies reporting the performance of biomarkers and cytology in detecting bladder cancer, sensitivity (95% CI) was highest for ImmunoCyt [84% (77% to 91%)] and lowest for cytology [44% (38% to 51%)], whereas specificity was highest for cytology [96% (94% to 98%)] and lowest for ImmunoCyt [75% (68% to 83%)]. In the cost-effectiveness analysis the most effective strategy in terms of true positive cases (44) and life-years (11.66) [flexible cystoscopy (CSC) and ImmunoCyt followed by PDD in initial diagnosis and CSC followed by WLC in follow-up] had an incremental cost per life-year of over 270,000 pounds. The least effective strategy [cytology followed by WLC in initial diagnosis (average cost over 20 years 1403 pounds, average life expectancy 11.59)] was most likely to be considered cost-effective when society's willingness to pay was less than 20,000 pounds per life-year. No strategy was cost-effective more than 50% of the time, but four of the eight strategies in the probabilistic sensitivity analysis (three involving a biomarker or PDD) were each associated with a 20% chance of being considered cost-effective. In sensitivity analyses the results were most sensitive to the pretest probability of disease (5% in the base case). CONCLUSIONS: The advantages of PDD's higher sensitivity in detecting bladder cancer have to be weighed against the disadvantages of a higher false-positive rate. Taking into account the assumptions made in the model, strategies involving biomarkers and/or PDD provide additional benefits at a cost that society might be willing to pay. Strategies replacing WLC with PDD provide more life-years but it is unclear whether they are worth the extra cost.

Economic evaluation of the treatment of grade II haemorrhoids: a comparison of stapled haemorrhoidopexy and rubber band ligation.

OBJECTIVES: Haemorrhoidal disease is a common condition causing considerable distress to individuals and significant cost to healthcare services. This paper explored the cost-effectiveness of stapled haemorrhoidopexy (SH) compared with the non-surgical intervention, rubber band ligation (RBL), for grade II symptomatic circumferential haemorrhoids. METHOD: An economic evaluation alongside a randomized controlled trial conducted between October 2002 and February 2005. Adults were recruited and randomized to either SH or RBL. The same surgeon performed all procedures and investigators were blinded until analyses were completed. Primary outcomes measured at 52 weeks were cumulative costs to the NHS, clinical diagnosis of recurrence and quality adjusted life years (QALYs). RESULTS: Sixty symptomatic men and women with confirmed clinical diagnosis of grade II symptomatic haemorrhoids were randomized. Loss to follow-up was up to 10% at 52 weeks. The mean cost for SH was greater than RBL (mean difference: 1483 pounds, 95% CI: 1339-1676); disease recurrence was lower (OR = 0.18, 95% CI: 0.03-0.86); and there was no evidence of a statistically significant difference in QALYs (-0.014, 95% CI: -0.076 to 0.051). SH was associated with a modest incremental cost per recurrence avoided at 12 months follow-up (4945 pounds). Based on current data, it was considered highly unlikely to be cost-effective in terms of incremental cost per QALY. CONCLUSIONS: There is insufficient evidence about the cost-effectiveness of SH for grade II haemorrhoids to recommend its routine use in place of RBL. Further information is needed from larger trials with a longer-term follow-up to inform subsequent economic evaluation.

A randomised controlled trial of the use of aciclovir and/or prednisolone for the early treatment of Bell's palsy: the BELLS study.

OBJECTIVE: To determine whether oral prednisolone or aciclovir, used separately or in combination, early in the course of Bell's palsy, improves the chances of recovery at 3 and 9 months. DESIGN: A 2 x 2 factorial randomised double-blind trial. Patients were randomly assigned to treatment by an automated telephone service using a permuted block randomisation technique with block sizes of four or eight, and no stratification. SETTING: Mainland Scotland, with referrals mainly from general practice to 17 hospital trial sites. PARTICIPANTS: Adults (aged 16 years or older) with unilateral facial nerve weakness of no identifiable cause presenting to primary care, the emergency department or NHS24 within 72 hours of symptom onset. INTERVENTIONS: Patients were randomised to receive active preparations or placebo for 10 days: (1) prednisolone (50 mg per day, 2 x 25-mg capsules) and aciclovir (2000 mg per day, 5 x 400-mg capsules); (2) prednisolone and placebo (lactose, indistinguishable); (3) aciclovir and placebo; and (4) placebo and placebo. OUTCOME MEASURES: The primary outcome was recovery of facial function assessed by the House-Brackmann scale. Secondary outcomes included health status, pain, self-perceived appearance and cost-effectiveness. RESULTS: Final outcomes were available for 496 patients, balanced for gender; mean age 44 years; initial facial paralysis moderate to severe. One half of patients initiated treatment within 24 hours of onset of symptoms, one-third within 24-48 hours and the remainder within 48-72 hours. Of the completed patients, 357 had recovered by 3 months and 80 at 9 months, leaving 59 with a residual deficit. There were significant differences in complete recovery at 3 months between the prednisolone comparison groups (83.0% for prednisolone, 63.6% for no prednisolone, a difference of + 19.4%; 95% confidence interval (CI): + 11.7% to + 27.1%, p < 0.001). The number needed to treat (NNT) in order to achieve one additional complete recovery was 6 (95% CI: 4 to 9). There was no significant difference between the aciclovir comparison groups (71.2% for aciclovir and 75.7% for no aciclovir). Nine-month assessments of patients recovered were 94.4% for prednisolone compared with 81.6% for no prednisolone, a difference of + 12.8% (95% CI: + 7.2% to + 18.4%, p < 0.001); the NNT was 8 (95% CI: 6 to 14). Proportions recovered at 9 months were 85.4% for aciclovir and 90.8% for no aciclovir, a difference of -5.3%. There was no significant prednisolone-aciclovir interaction at 3 months or at 9 months. Outcome differences by individual treatment (the four-arm model) showed significant differences. At 3 months the recovery rate was 86.3% in the prednisolone treatment group, 79.7% in the aciclovir-prednisolone group, 64.7% in the placebo group and 62.5% in the aciclovir group. At 9 months the recovery rates were respectively 96.1%, 92.7%, 85.3% and 78.1%. The increase in recovery rate conferred by the addition of prednisolone (both for prednisolone over placebo and for aciclovir-prednisolone over aciclovir) is highly statistically significant (p < 0.001). There were no significant differences in secondary measures apart from Health Utilities Index Mark 3 (HUI3) at 9 months in those treated with prednisolone. CONCLUSIONS: This study provided robust evidence to support the early use of oral prednisolone in Bell's palsy as an effective treatment which may be considered cost-effective. Treatment with aciclovir, either alone or with steroids, had no effect on outcome.