Systematic review of patient-reported outcome measures in patients with varicose veins.

BACKGROUND: Varicose veins can affect quality of life. Patient-reported outcome measures (PROMs) provide a direct report from the patient about the impact of the disease without interpretation from clinicians or anyone else. The aim of this study was to examine the quality of the psychometric evidence for PROMs used in patients with varicose veins. METHODS: A systematic review was undertaken to identify studies that reported the psychometric properties of generic and disease-specific PROMs in patients with varicose veins. Literature searches were conducted in databases including MEDLINE, up to July 2016. The psychometric criteria used to assess these studies were adapted from published recommendations in accordance with US Food and Drug Administration guidance. RESULTS: Nine studies were included which reported on aspects of the development and/or validation of one generic (36-Item Short Form Health Survey, SF-36®) and three disease-specific (Aberdeen Varicose Vein Questionnaire, AVVQ; Varicose Veins Symptoms Questionnaire, VVSymQ®; Specific Quality-of-life and Outcome Response - Venous, SQOR-V) PROMs. The evidence from included studies provided data to support the construct validity, test-retest reliability and responsiveness of the AVVQ. However, its content validity, including weighting of the AVVQ questions, was biased and based on the opinion of clinicians, and the instrument had poor acceptability. VVSymQ® displayed good responsiveness and acceptability rates. SF-36® was considered to have satisfactory responsiveness and internal consistency. CONCLUSION: There is a scarcity of psychometric evidence for PROMs used in patients with varicose veins. These data suggest that AVVQ and SF-36® are the most rigorously evaluated PROMs in patients with varicose veins.

Systematic review of carotid artery procedures and the volume-outcome relationship in Europe.

BACKGROUND: Hospitals that conduct more procedures on the carotid arteries may achieve better outcomes. In the context of ongoing reconfiguration of UK vascular services, this systematic review was conducted to evaluate the relationship between the volume of carotid procedures and outcomes, including mortality and stroke. METHODS: Searches of electronic databases identified studies that reported the effect of hospital or clinician volume on outcomes. Reference and citation searches were also performed. Inclusion was restricted to European populations on the basis that the model of healthcare delivery is similar across Europe, but differs from that in the USA and elsewhere. Analyses of hospital and clinician volume, and carotid endarterectomy (CEA) and carotid artery stenting (CAS) were conducted separately. RESULTS: Eleven eligible studies were identified (233 411 participants), five from the UK, two from Sweden, one each from Germany, Finland and Italy, and a combined German, Austrian and Swiss population. All studies were observational. Two large studies (179 736 patients) suggested an inverse relationship between hospital volume and mortality (number needed to treat (NNT) as low as 165), and combined mortality and stroke (NNT as low as 93), following CEA. The evidence was less clear for CAS; multiple analyses in three studies did not identify convincing evidence of an association. Limited data are available on the relationship between clinician volume and outcome in CAS; in CEA, an inverse relationship was identified by two of three small studies. CONCLUSION: The evidence from the largest and highest-quality studies included in this review support the centralization of CEA.

Systematic review assessing the measurement properties of patient-reported outcomes for venous leg ulcers.

BACKGROUND: A variety of instruments have been used to assess outcomes for patients with venous leg ulcers. This study sought to identify, evaluate and recommend the most appropriate patient-reported outcome measures (PROMs) for English-speaking patients with venous leg ulcers. METHODS: This systematic review used a two-stage search approach. Electronic searches of major databases including MEDLINE were completed in October 2015, and then updated in July 2016. Additional studies were identified from citation checking. Study selection, data extraction and quality assessment were undertaken independently by at least two reviewers. Evaluation and summary of measurement properties of identified PROMs were done using standard and adapted study-relevant criteria. RESULTS: Ten studies with data for four generic PROMS and six condition-specific measures were identified. No generic PROM showed adequate content and criterion validity; however, the EuroQoL Five Dimensions (EQ-5D™), Nottingham Health Profile (NHP) and 12-item Short-Form Health Survey (SF-12®) had good acceptability. In general, the EQ-5D™ showed poor responsiveness in patients with venous leg ulcers. Most condition-specific PROMs demonstrated poor criterion and construct validity. Overall, there was some evidence of internal consistency for the Venous Leg Ulcer Quality of Life (VLU-QoL) and the Sheffield Preference-based Venous Ulcer questionnaire (SPVU-5D). Test-retest reliability was satisfactory for the Venous Leg Ulcer Self-Efficacy Tool (VeLUSET). CONCLUSION: The NHP and VLU-QoL questionnaire seemed the most suitable PROMs for use by clinicians. However, a valid condition-specific PROM is still required.

Systematic review and qualitative evidence synthesis of patient-reported outcome measures for abdominal aortic aneurysm.

BACKGROUND: The aim was to identify and evaluate existing patient-reported outcome measures (PROMs) for use in patients with an abdominal aortic aneurysm (AAA) to inform the selection for use in surgical practice. METHODS: Two reviews were conducted: a systematic review to identify valid, reliable and acceptable PROMs for patients with an AAA, and a qualitative evidence synthesis to assess the relevance to patients of the identified PROM items. PROM studies were evaluated for their psychometric properties using established assessment criteria, and for their methodological quality using the COSMIN checklist. Qualitative studies were synthesized using framework analysis, and concepts identified were then triangulated using a protocol with the item concepts of the identified PROMs. RESULTS: Four PROMs from three studies were identified in the first review: Short Form 36, Australian Vascular Quality of Life Index, Aneurysm Dependent Quality of Life (AneurysmDQoL) and Aneurysm Symptoms Rating Questionnaire (AneurysmSRQ). None of the identified PROMs had undergone a rigorous psychometric evaluation within the AAA population. Four studies were included in the qualitative synthesis, from which 28 concepts important to patients with an AAA were identified. The AneurysmDQoL and AneurysmSRQ together provided the most comprehensive assessment of these concepts. Fear of rupture, control, ability to forget about the condition and size of aneurysm were all concepts identified in the qualitative studies but not covered by items in the identified PROMs. CONCLUSION: Further research is needed to develop PROMs for AAA that are reliable, valid and acceptable to patients.

Procedure Volume and the Association with Short-term Mortality Following Abdominal Aortic Aneurysm Repair in European Populations: A Systematic Review.

OBJECTIVE: To evaluate the relationship between the volume of abdominal aortic aneurysm (AAA) procedures undertaken and the primary outcome of mortality in Europe. Previous systematic reviews of this relationship are outdated and are overwhelmingly based on US data. DATA SOURCES: Comprehensive searching within MEDLINE and other bibliographic databases supplemented by citation searching and hand-searching of journals was undertaken to identify studies that reported the effect of hospital or clinician volume on any reported outcomes in adult, European populations, undergoing AAA repair and published in the last 10 years. METHODS: Two reviewers conducted study selection with independent, duplicate data extraction and quality assessment. A planned meta-analysis was not conducted because of the high risk of bias, the likelihood of individual study subjects being included in more than one study and diversity in the clinical populations studied and methods used. RESULTS: Sixteen studies (n = 237,074 participants) from the UK (n = 11 studies), Germany (n = 3 studies), Norway (n = 1 study), and one from the UK and Sweden were included. Data in the included studies came from administrative databases and clinical registries incorporating a variety of clinical and procedural groups; the study quality was limited by the use of observational study designs. Overall, the evidence favoured the existence of an inverse volume outcome relationship between hospital volume and mortality. Insufficient evidence was available to reach conclusions on the relationship between clinician volume and outcome and between hospital or clinician volume and secondary outcomes including complications and length of hospital stay. CONCLUSIONS: The evidence from this review suggests a relationship between the hospital volume of AAA procedures conducted and short-term mortality; however, as volume typically represents a complex amalgamation of factors further research will be useful to identify the core characteristics of volume that influence improved outcomes.

Evidence Review Group approaches to the critical appraisal of manufacturer submissions for the NICE STA process: a mapping study and thematic analysis.

BACKGROUND: The National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process was set up as a rapid way to appraise new technologies for use within the NHS in England and Wales and has been in place since 2005. OBJECTIVES: This study had five primary objectives: (1) to provide a map of the STA process to date; (2) to identify current approaches to the critical appraisal of manufacturers' submissions (MSs) by Evidence Review Groups (ERGs); (3) to identify recurring themes in clarification letters sent to manufacturers; (4) to provide recommendations for possible alternative approaches to be used in the critical appraisal process; and (5) to revise the current ERG report template. DATA SOURCES: Data for the mapping of the STA process were obtained from the NICE website (www.nice.org.uk). Data for the analyses of the ERG reports and clarification letters were taken from the reports and letters themselves. REVIEW METHODS: For the mapping, a spreadsheet was developed to collect data on 22 predefined variables related to timings and outcomes. Simple descriptive statistics were used to analyse the data. For the thematic analysis, a documentary analysis of 30 ERG reports was undertaken. Data on key elements of the MSs, the processes undertaken by ERGs and the strengths and weaknesses of MSs were extracted. A framework of a priori themes was developed. Data were extracted, coded and analysed according to a framework approach. Twenty-one clarification letters were examined and data were extracted using a set of codes to cover report quality, systematic review methods and clinical/economic issues. The current ERG report template was modified and sent to the current ERG teams for comment. All comments were considered and formed the basis for further revisions to the template. RESULTS: Ninety-five STAs were included in the mapping exercise. Many STAs were subject to delay or cancellation for a variety of reasons. The ERG reports highlighted the strengths and weaknesses of MSs to the STA process. Thematic analysis of these data offered a means of clarifying and describing these aspects of the submissions. This analysis generated five themes: process, reporting, satisfaction of objectives, reliability and validity of findings, and content. Points from clarification letters were analysed and presented in four main categories: report quality, systematic review methods, clinical data analysis and economic data analysis. LIMITATIONS: Nearly all data were obtained from the NICE website; therefore, any errors in the data on the website will be reflected in the mapping analysis presented in this report. Missing data for the mapping exercise limit the generalisability of the findings. Analyses were limited to what was reported in the ERG reports and the clarification letters. CONCLUSIONS: Guidance suggested for manufacturers will help to ensure that more appropriate submissions are received in the future while recommendations provided for ERG teams will help to guide teams to ensure that reporting methods are transparent. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The clinical effectiveness and safety of prophylactic retinal interventions to reduce the risk of retinal detachment and subsequent vision loss in adults and children with Stickler syndrome: a systematic review.

BACKGROUND: Stickler syndrome, also known as hereditary progressive arthro-ophthalmopathy, is an inherited progressive disorder of the collagen connective tissues. Manifestations include short-sightedness, cataracts, retinal problems leading to retinal detachment and possible blindness. This is principally the case among individuals with type 1 Stickler Syndrome. It is the most commonly identified inherited cause of retinal detachment in childhood. However, there is no consensus regarding best practice and no current guidelines on prophylactic interventions for this population. OBJECTIVES: The aim of this systematic review was to assess the evidence for the clinical effectiveness and safety of primary prophylactic interventions for the prevention of retinal detachment in previously untreated eyes without retinal detachment in patients with Stickler syndrome. The primary outcome of interest was retinal detachment post prophylaxis. DATA SOURCES: A systematic search was made of 11 databases of published and unpublished literature, which included MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing and Allied Health Literature and The Cochrane Library. There was no restriction by language or date. The references of all included studies were checked for further relevant citations and authors of studies with potentially relevant data were also contacted. REVIEW METHODS: Two reviewers double-screened all titles and abstracts of the citations retrieved by the search to identify studies that satisfied the inclusion criteria. Both reviewers also independently extracted and quality assessed all included studies. A narrative synthesis was performed. RESULTS: The literature search identified 1444 unique citations, of which four studies satisfied the inclusion criteria. The two principal studies were both retrospective cohort studies with control groups in populations with type 1 Stickler syndrome. One study evaluated 360° cryotherapy (n = 204) and the other focal or circumferential laser treatment (n = 22). Both studies reported a statistically significant difference in the rate of retinal detachment per eye between the groups receiving prophylaxis and the controls. However, both studies were subject to a high risk of bias. The results of the two supporting studies of Wagner-Stickler patients were either relatively inconsistent or unreliable. No study reported any major or long-term complications associated with the interventions. Despite the weaknesses of the evidence, the rate of retinal detachment in the intervention groups, especially the cryotherapy group, was lower than the rate either experienced in the study control groups or reported in other studies of untreated Stickler syndrome populations not exposed to prophylaxis. CONCLUSIONS: Only 360° cryotherapy and focal and circumferential laser treatment have been evaluated for the type 1 Stickler syndrome population, and then only by a single retrospective, controlled, cohort study in each case. Both of these studies report a significant difference between intervention and control groups (principally no treatment) and no major or long-term side effects or complications. However, there is a high risk of bias within these two studies, so the relative effectiveness of either intervention is uncertain. FUTURE WORK: A service priority is to determine reliably the prevalence of Stickler syndrome, i.e. how many individuals have type 1 or type 2 Stickler syndrome, and their risk of retinal detachment and subsequent blindness. A non-randomised, prospective cohort comparison study, in which eligible participants are treated, followed-up and analysed in one of three study arms, for no treatment, laser therapy or cryotherapy, would potentially offer further certainty in terms of the relative efficacy of both prophylaxis versus no prophylaxis and cryotherapy versus laser therapy than is possible with the currently available data. Alternatively, continued follow-up and analysis of existing study data, and data collection from relevant sample populations, are required to assess the long-term risks of blindness, retinal detachment and prophylaxis. FUNDING: This study was funded by the National Institute for Health Research Health Technology Assessment programme.

Amblyopia and quality of life: a systematic review.

Amblyopia is a common condition, which can affect up to 5% of the general population. Health-related quality-of-life (HRQoL) implications of amblyopia and/or its treatment have been explored in the literature. A systematic literature search was undertaken during the period of 7-14 May 2010 to identify the HRQoL implications of amblyopia and/or its treatment. A total of 35 papers were included in the literature review. The HRQoL implications of amblyopia related specifically to amblyopia treatment, rather than to the condition itself. These included impact on family life, social interactions, difficulties in undertaking daily activities, as well as feelings and behaviour. The identified studies adopted a number of methodologies. The study populations included children with the condition, parents of children with amblyopia, and adults who had undertaken amblyopia treatment as a child. Some studies developed their own measures of HRQoL, and others determined HRQoL through proxy measures. The reported findings of the HRQoL implications are of importance when considering the management of cases of amblyopia. The issues identified in the literature review are discussed with respect to how HRQoL is measured (treatment compliance vs proxy measures), and whether HRQoL is taken from a child's or a parent's perspective. Changing societal views over glasses and occlusion therapy are also discussed. Further research is required to assess the immediate and long-term effects of amblyopia and/or its treatment on HRQoL using a more standardised approach.

Avoiding and identifying errors in health technology assessment models: qualitative study and methodological review.

BACKGROUND: Health policy decisions must be relevant, evidence-based and transparent. Decision-analytic modelling supports this process but its role is reliant on its credibility. Errors in mathematical decision models or simulation exercises are unavoidable but little attention has been paid to processes in model development. Numerous error avoidance/identification strategies could be adopted but it is difficult to evaluate the merits of strategies for improving the credibility of models without first developing an understanding of error types and causes. OBJECTIVES: The study aims to describe the current comprehension of errors in the HTA modelling community and generate a taxonomy of model errors. Four primary objectives are to: (1) describe the current understanding of errors in HTA modelling; (2) understand current processes applied by the technology assessment community for avoiding errors in development, debugging and critically appraising models for errors; (3) use HTA modellers' perceptions of model errors with the wider non-HTA literature to develop a taxonomy of model errors; and (4) explore potential methods and procedures to reduce the occurrence of errors in models. It also describes the model development process as perceived by practitioners working within the HTA community. DATA SOURCES: A methodological review was undertaken using an iterative search methodology. Exploratory searches informed the scope of interviews; later searches focused on issues arising from the interviews. Searches were undertaken in February 2008 and January 2009. In-depth qualitative interviews were performed with 12 HTA modellers from academic and commercial modelling sectors. REVIEW METHODS: All qualitative data were analysed using the Framework approach. Descriptive and explanatory accounts were used to interrogate the data within and across themes and subthemes: organisation, roles and communication; the model development process; definition of error; types of model error; strategies for avoiding errors; strategies for identifying errors; and barriers and facilitators. RESULTS: There was no common language in the discussion of modelling errors and there was inconsistency in the perceived boundaries of what constitutes an error. Asked about the definition of model error, there was a tendency for interviewees to exclude matters of judgement from being errors and focus on 'slips' and 'lapses', but discussion of slips and lapses comprised less than 20% of the discussion on types of errors. Interviewees devoted 70% of the discussion to softer elements of the process of defining the decision question and conceptual modelling, mostly the realms of judgement, skills, experience and training. The original focus concerned model errors, but it may be more useful to refer to modelling risks. Several interviewees discussed concepts of validation and verification, with notable consistency in interpretation: verification meaning the process of ensuring that the computer model correctly implemented the intended model, whereas validation means the process of ensuring that a model is fit for purpose. Methodological literature on verification and validation of models makes reference to the Hermeneutic philosophical position, highlighting that the concept of model validation should not be externalized from the decision-makers and the decision-making process. Interviewees demonstrated examples of all major error types identified in the literature: errors in the description of the decision problem, in model structure, in use of evidence, in implementation of the model, in operation of the model, and in presentation and understanding of results. The HTA error classifications were compared against existing classifications of model errors in the literature. A range of techniques and processes are currently used to avoid errors in HTA models: engaging with clinical experts, clients and decision-makers to ensure mutual understanding, producing written documentation of the proposed model, explicit conceptual modelling, stepping through skeleton models with experts, ensuring transparency in reporting, adopting standard housekeeping techniques, and ensuring that those parties involved in the model development process have sufficient and relevant training. Clarity and mutual understanding were identified as key issues. However, their current implementation is not framed within an overall strategy for structuring complex problems. LIMITATIONS: Some of the questioning may have biased interviewees responses but as all interviewees were represented in the analysis no rebalancing of the report was deemed necessary. A potential weakness of the literature review was its focus on spreadsheet and program development rather than specifically on model development. It should also be noted that the identified literature concerning programming errors was very narrow despite broad searches being undertaken. CONCLUSIONS: Published definitions of overall model validity comprising conceptual model validation, verification of the computer model, and operational validity of the use of the model in addressing the real-world problem are consistent with the views expressed by the HTA community and are therefore recommended as the basis for further discussions of model credibility. Such discussions should focus on risks, including errors of implementation, errors in matters of judgement and violations. Discussions of modelling risks should reflect the potentially complex network of cognitive breakdowns that lead to errors in models and existing research on the cognitive basis of human error should be included in an examination of modelling errors. There is a need to develop a better understanding of the skills requirements for the development, operation and use of HTA models. Interaction between modeller and client in developing mutual understanding of a model establishes that model's significance and its warranty. This highlights that model credibility is the central concern of decision-makers using models so it is crucial that the concept of model validation should not be externalized from the decision-makers and the decision-making process. Recommendations for future research would be studies of verification and validation; the model development process; and identification of modifications to the modelling process with the aim of preventing the occurrence of errors and improving the identification of errors in models.

Rivaroxaban for the prevention of venous thromboembolism: a single technology appraisal.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of rivaroxaban for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from four randomised controlled trials (RCTs) comparing rivaroxaban with enoxaparin [RECORD (Regulation of Coagulation in Orthopedic surgery to pRevent Deep venous thrombosis and pulmonary embolism) 1-4] and three comparing dabigatran with enoxaparin [RE-NOVATE (the prevention of venous thromboembolism after total hip replacement trial), RE-MODEL (the prevention of venous thromboembolism after total knee replacement trial) and RE-MOBILIZE (the prevention of venous thromboembolism after total knee arthroplasty trial)]. The evidence from the four RECORD trials indicates that rivaroxaban had superior efficacy over enoxaparin after total hip replacement (THR) and total knee replacement (TKR). For the composite primary outcome of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and death from all causes the relative risk reductions were 70-79% in THR and 31-49% in TKR. Rivaroxaban also had superior efficacy over enoxaparin for the secondary outcome major VTE. Rivaroxaban was not inferior to enoxaparin on the safety outcome of major bleeding. After the correction of some errors found by the ERG, the manufacturer's economic model represented a reasonable model of patients receiving prophylaxis for THR or TKR. In the base-case analyses rivaroxaban dominated both enoxaparin and dabigatran. The incremental costs saved and quality-adjusted life-years (QALYs) gained were small (below 200 pounds and 0.005, respectively, per person). Analyses were conducted sampling from the distributions observed from the RCTs. When all parameters were sampled rivaroxaban dominated enoxaparin in all scenarios except for two, in which enoxaparin produced more QALYs than rivaroxaban and had an incremental cost per QALY gained of 5000 pounds and 8000 pounds respectively. Rivaroxaban dominated dabigatran when RECORD 1 and RECORD 2, individually or pooled, were compared with RE-NOVATE and when all four rivaroxaban RCTs pooled were compared with all three dabigatran RCTs. Dabigatran dominated rivaroxaban comparing RECORD 4 with RE-MODEL and RE-MOBILIZE, and was more cost-effective than rivaroxaban comparing RECORD 3 (incremental cost per QALY gained of rivaroxaban compared with dabigatran of 123,000 pounds) or RECORD 3 and RECORD 4 pooled (incremental cost per QALY gained of dabigatran compared with rivaroxaban of 400 pounds) with RE-MODEL and RE-MOBILIZE. In conclusion, the evidence indicates that rivaroxaban is not inferior to enoxaparin in terms of the primary and secondary outcomes. The submission presents a reasonable estimation of the cost-effectiveness of rivaroxaban compared with enoxaparin and dabigatran, although the uncertainty in the decision has been underestimated. The results are particularly sensitive to any assumed difference in the number of fatal PEs, but the ERG does not believe there is sufficient evidence to support a difference between interventions. The NICE guidance issued as a result of the STA states that: riveroxaban, within its marketing authorisation, is recommended as an option for the prevention of venous thromboembolism in adults having elective THR or elective TKB.

The acceptability to patients of computerized cognitive behaviour therapy for depression: a systematic review.

BACKGROUND: Cognitive behaviour therapy (CBT) is widely used to treat depression. However, CBT is not always available to patients because of a shortage of therapists and long waiting times. Computerized CBT (CCBT) is one of several alternatives currently available to treat patients with depression. Evidence of its clinical effectiveness has led to programs being used increasingly within the UK and elsewhere. However, little information is available regarding the acceptability of CCBT to patients. METHOD: A systematic review of sources of information on acceptability to patients of CCBT for depression. RESULTS: Sources of information on acceptability included: recruitment rates, patient drop-outs and patient-completed questionnaires. We identified 16 studies of CCBT for the treatment of depression that provided at least some information on these sources. Limited information was provided on patient take-up rates and recruitment methods. Drop-out rates were comparable to other forms of treatment. Take-up rates, when reported, were much lower. Six of the 16 studies included specific questions on patient acceptability or satisfaction although information was only provided for those who had completed treatment. Several studies have reported positive expectancies and high satisfaction in routine care CCBT services for those completing treatment. CONCLUSIONS: Trials of CCBT should include more detailed information on patient recruitment methods, drop-out rates and reasons for dropping out. It is important that well-designed surveys and qualitative studies are included alongside trials to determine levels and determinants of patient acceptability.

Computerised cognitive behaviour therapy for depression and anxiety update: a systematic review and economic evaluation.

OBJECTIVES: To evaluate computerised cognitive behaviour therapy (CCBT) for the treatment of anxiety, depression, phobias, panic and obsessive-compulsive behaviour (OCD). The software packages to be considered include Beating the Blues (BtB), Overcoming Depression: a five areas approach, FearFighter (FF), Cope and BT Steps. Other packages or programmes incorporating CCBT were also considered. DATA SOURCES: Electronic databases from 1966 to March 2004. Evidence submitted by sponsors for CCBT products. REVIEW METHODS: A systematic review was a review of the literature and the evidence submitted by sponsors for each of the products. A series of cost-effectiveness models was developed and run by the project team for the five CCBT products across the three mental health conditions. RESULTS: Twenty studies were identified in the clinical effectiveness review. The analysis of these results showed some evidence that CCBT is as effective as therapist-led cognitive behaviour therapy (TCBT) for the treatment of depression/anxiety and phobia/panic and is more effective than treatment as usual (TAU) in the treatment of depression/anxiety. CCBT also appears to reduce therapist time compared with TCBT. When reviewing cost-effectiveness studies, only one published economic evaluation of CCBT was found. This was an economic evaluation of the depression software BtB alongside a randomised controlled trial (RCT), which found that BtB was cost-effective against TAU in terms of cost per quality-adjusted life-year (QALY) (less than 2000 pounds), however it contained weaknesses that were then addressed in the cost-effectiveness model developed for the study. The results of the model for the depression software packages in terms of incremental cost per QALY compared with TAU and the chance of being cost-effective at 30,000 pounds per QALY were for BtB 1801 pounds and 86.8%, for Cope 7139 pounds and 62.6% and for Overcoming Depression 5391 pounds and 54.4%. The strength of the BtB software being that it has been evaluated in the context of an RCT with a control group. The subgroup analysis found no differences across the severity groupings. For phobia/panic software, the model showed an incremental cost per QALY of FF over relaxation was 2380 pounds. Its position compared with TCBT is less clear. When modelling OCD packages, using the practice-level licence cost meant that BT Steps was dominated by TCBT, which had significantly better outcomes and was cheaper. However, the cheaper PCT licence resulted in the incremental cost-effectiveness of BT Steps over relaxation being 15,581 pounds and TCBT over BT Steps being 22,484 pounds. CONCLUSIONS: The study findings are subject to substantial uncertainties around the organisational level for purchasing these products and the likely throughput. This is in addition to concerns with the quality of evidence on response to therapy, longer term outcomes and quality of life. The position of CCBT within a stepped care programme needs to be identified, as well as its relationship to other efforts to increase access to CBT and psychological therapies. Research is needed to compare CCBT with other therapies that reduce therapist time, in particular bibliotherapy and to explore the use of CCBT via the Internet. Independent research is needed, particularly RCTs, that examine areas such as patient preference and therapist involvement within primary care.

The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer.

Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of tegafur and uracil administered together with leucovorin. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of these oral therapies against standard intravenous 5-fluorouracil regimens. A systematic literature review was conducted to assess the clinical effectiveness of the therapies and costs were calculated from the UK National Health Service perspective for drug acquisition, drug administration, and the treatment of adverse events. A cost-minimisation analysis was used; this assumes that the treatments are of equal efficacy, although direct randomised controlled trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available. The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (Pounds 2132) and tegafur with uracil (Pounds 3385) were lower than costs for the intravenous Mayo regimen (Pounds 3593) and infusional regimens on the de Gramont (Pounds 6255) and Modified de Gramont (Pounds 3485) schedules over the same treatment period. Oral therapies result in lower costs to the health service than intravenous therapies. Further research is needed to determine the relative clinical effectiveness of oral therapies vs infusional regimens.

A systematic review and economic evaluation of magnetic resonance cholangiopancreatography compared with diagnostic endoscopic retrograde cholangiopancreatography.

OBJECTIVES: To compare the clinical and cost-effectiveness of magnetic resonance cholangiopancreatography (MRCP) with diagnostic endoscopic retrograde cholangiopancreatography (ERCP) for the investigation of biliary obstruction. DATA SOURCES: Electronic bibliographic databases, the reference lists of relevant articles and various health services research-related resources. REVIEW METHODS: The data sources were searched and selected studies were assessed using quality criteria. In total, 28 prospective diagnostic studies were identified reporting several suspected conditions plus one of patient satisfaction. Analyses were then performed to establish sensitivities, specificities, likelihood ratios and confidence intervals. The relative cost-effectiveness of adopting MRCP scanning in the investigation of the biliary tree was undertaken using a probabilistic economic model. RESULTS: The median sensitivity for choledocholithiasis (13 studies) was 93% and the median specificity 94%. The median likelihood ratio for a positive value was 15.75 and for a negative value 0.08. Reported sensitivities for malignancy were somewhat lower, ranging from 81 to 86%, and specificities ranged from 92 to 100%. There was some evidence that MRCP is an accurate diagnostic test in comparison to ERCP, although the quality of studies was moderate. Claustrophobia prevented at least some patients from having MRCP in ten of the 28 studies. The other 18 studies did not mention claustrophobia. The probability of avoiding unnecessary diagnostic ERCP is estimated at 30%. These patients could avoid the unnecessary risk of complications and death associated with diagnostic ERCP, and substantial cost saving would be gained. The overall expected cost saving associated with MRCP is GBP149; the overall expected gain in quality-adjusted life-year is estimated at 0.011. CONCLUSIONS: There is some evidence that MRCP is an accurate investigation compared with diagnostic ERCP, although the values for malignancy compared with choledocholithiasis were somewhat lower. The quality of studies was moderate. The limited evidence on patient satisfaction showed that patients preferred MRCP to diagnostic ERCP. The estimated clinical and economic impacts of diagnostic MRCP versus diagnostic ERCP are very favourable. The baseline estimate is that MRCP may both reduce cost and result in improved quality of life outcomes compared with diagnostic ERCP. Further research is suggested to compare MRCP and diagnostic ERCP with final diagnosis and also with the full range of target conditions; to examine patient satisfaction and ways of reducing problems with claustrophobia; to look at protocols to help identify who could most benefit from MRCP or ERCP; to assess the relative need and urgency of patient access to magnetic resonance imaging services, and also to determine how demand would affect availability and potential cost savings.

Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of capecitabine and tegafur with uracil (UFT/LV) as first-line treatments for patients with metastatic colorectal cancer, as compared with 5-fluorouracil/folinic acid (5-FU/FA) regimens. DATA SOURCES: Electronic databases, reference lists of relevant articles and sponsor submissions were also consulted. REVIEW METHODS: Systematic searches, selection against criteria and quality assessment were performed to obtain data from relevant studies. Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to compare the cost-effectiveness of capecitabine and UFT/LV with three intravenous 5-FU/LV regimens widely used in the UK: the Mayo, the modified de Gramont regimen and the inpatient de Gramont regimens. RESULTS: The evidence suggests that treatment with capecitabine improves overall response rates and has an improved adverse effect profile in comparison with 5-FU/LV treatment with the Mayo regimen, with the exception of hand-foot syndrome. Time to disease progression or death after treatment with UFT/LV in one study appears to be shorter than after treatment with 5-FU/LV with the Mayo regimen, although it also had an improved adverse effect profile. Neither capecitabine nor UFT/LV appeared to improve health-related quality of life. Little information on patient preference was available for UFT/LV, but there was indicated a strong preference for this over 5-FU/LV. The total cost of capecitabine and UFT/LV treatments were estimated at 2111 pounds and 3375 pounds, respectively, compared with the total treatment cost for the Mayo regimen of 3579 pounds. Cost estimates were also presented for the modified de Gramont and inpatient de Gramont regimens. These were 3684 pounds and 6155 pounds, respectively. No survival advantage was shown in the RCTs of the oral drugs against the Mayo regimen. Cost savings of capecitabine and UFT/LV over the Mayo regimen were estimated to be 1461 pounds and 209 pounds, respectively. Drug acquisition costs were higher for the oral therapies than for the Mayo regimen, but were offset by lower administration costs. Adverse event treatment costs were similar across the three regimens. It was inferred that there was no survival difference between the oral drugs and the de Gramont regimens. Cost savings of capecitabine and UFT/LV over the modified de Gramont regimen were estimated to be 1353 pounds and 101 pounds, respectively, and over the inpatient de Gramont regimen were estimated to be 4123 pounds and 2870 pounds, respectively. CONCLUSIONS: The results show that there are cost savings associated with the use of oral therapies. No survival difference has been proven between the oral drugs and the Mayo regimen. In addition, no evidence of a survival difference between the Mayo regimen and the de Gramont regimens has been identified. However, improved progression-free survival and an improved adverse event profile have been shown for the de Gramont regimen over the Mayo regimen. Further research is recommended into the following areas: quality of life data should be included in trials of colorectal cancer treatments; the place of effective oral treatments in the treatment of colorectal cancer, the safety mechanisms needed to ensure compliance and the monitoring of adverse effects; the optimum duration of treatment; the measurement of patient preference; and a phase III comparative trial of capecitabine and UFT/LV versus modified de Gramont treatment to determine whether there was any survival advantage and to collate the necessary economic data.

Monitoring the care of lung cancer patients: linking audit and care pathways.

Clinical audit plays an important role in monitoring the provision of care for patients whatever their condition. Care pathways define the steps and expected course of events in the care of patients with a specific clinical problem over a set time scale. This paper describes a study undertaken in a multisite cancer unit to develop a tool for monitoring the progress of lung cancer patients through a care pathway and auditing key standards within the pathway. Important issues associated with the development of this tool are highlighted. The process of developing this tool involved the following steps: a review of the literature dealing with the management of lung cancer patients; interviews with key personnel in primary, secondary, tertiary and palliative care; development of a paper-based series of forms representing key steps in the patient's care pathway; 3-month trial of the paper-based tool; analysis of completion rates and interviews with form users to evaluate effectiveness; and recommendations for creating an electronic record using the experience and lessons learned from the paper version. The paper forms developed through this multistage process were found to be acceptable to users and have the potential to provide accurate information at key points for audit throughout the patient's time within the health-care system for their lung cancer condition. The flexibility of this methodology allows it to be adapted readily to a variety of clinical situations and conditions.

Treatment of irritable bowel syndrome: a review of randomised controlled trials.

Irritable bowel syndrome (IBS) is a common chronic disorder that is associated with significant disability and health care costs. The purpose of this paper is to review and assess published randomised controlled trials examining the clinical effectiveness of interventions for IBS for 1987-1998. A literature search was conducted to identify randomised controlled trials of IBS treatments: 45 studies were identified that described randomised controlled trials and of these, six fulfilled all three criteria used to assess the quality of randomised controlled trials, as described by Jadad and colleagues.(1) These criteria are: adequate description of randomisation, double blinding, and description of withdrawals and dropouts. It is concluded that there are few studies which offer convincing evidence of effectiveness in treating the IBS symptom complex. This review strongly suggests that future work should include well designed trials that: describe the randomisation method; use internationally approved diagnostic criteria; and are double blinded and placebo controlled. Clear well defined outcome measures are necessary. Inclusion of quality of life measures allows comparison between trials in different therapeutic areas. Conducting such studies will help to overcome some of the difficulties identified in this review.

How effective are prevention strategies in reducing the prevalence of pressure ulcers?

The prevalence of pressure ulcers has remained constant at about 7% over the past 20 years, even though considerable time and money has been invested in various prevention strategies. This literature review explores whether pressure-prevention programmes can reduce the prevalence rate still lower or whether they are working but are limited by an increasingly aged population and rising patient acuity.