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 costeffectiveness 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 Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions.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 healthrelated 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 and £3375, respectively, compared with the total treatment cost for the Mayo regimen of £3579. Cost estimates were also presented for the modified de Gramont and inpatient de Gramont regimens. These were £3684 and £6155, 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 and £209, 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 and £101, respectively, and over the inpatient de Gramont regimen were estimated to be £4123 and £2870, 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

Barriers and Facilitators to the Implementation of Interventions to Prevent Youth Violence in Latin America: A Systematic Review and Qualitative Evidence Synthesis

Youth violence in Latin America is an important public health problem. However, the evidence from preventive programs within the region to address this problem is limited. Identifying context-specific factors that facilitate or hinder the success of interventions is necessary to guarantee the successful implementation of new preventive strategies. We present a systematic review and synthesis of qualitative studies to identify factors affecting the implementation of programs to prevent youth violence in Latin America. We searched 10 electronic databases and websites of international institutions. The quality of the studies was assessed using the critical appraisal skills program checklist, while the certainty of the findings of the synthesis was assessed using the certainty of the qualitative evidence approach. We included eight papers describing five programs in Argentina, Venezuela, Peru, El Salvador, and Mexico. Most of the factors affecting the implementation of programs were aspects related to features of the programs and social/political constraints. The synthesis suggests that future programs can benefit from having a multidisciplinary and/or multisectoral approach involving different key players. At the same time, potential strategies for avoiding problems related to such active engagement should be planned via promoting effective channels for communication and supervision. The review also suggests the importance of increasing awareness and motivation toward the problem of youth violence among relevant agencies and stakeholders. While the limited volume and quality of the literature impact on the ability to draw conclusions, the results could be useful for new programs being designed and the ones seeking to be adapted from other contexts

Choice and judgement in developing models for health technology assessment; a qualitative study

Introduction: The role of models in supporting health policy decisions is reliant on model credibility. Credibility is fundamentally determined by the choices and judgements that people make in the process of developing a model. However, the method of uncovering choices and making judgements in model development is largely unreported and is not addressed by modelling methods guidance. Methods: This qualitative study was part of a project examining errors in health technology assessment models. In-depth interviews with academic and commercial modellers were used to obtain descriptions of the model development process. Data were analysed using framework analysis and interpreted in the context of the methodological literature. Results: The activities involved in developing models were characterised according to the themes; understanding the decision problem, conceptual modelling, model implementation, model checking, and engaging with the decision maker. Finding and using evidence was frequently mentioned across these themes. There was marked variation between practitioners in the extent to which conceptual modelling was recognised as an activity distinct from model implementation. Discussion: Methodological approaches to addressing model credibility described in the wider modelling literature highlight the necessity to disentangle the conceptual modelling and implementation activities. Whilst interviewees talked of judgements and choice making throughout model development, discussion indicated that these were based upon skills and experience with no discussion of formal approaches. Methods are required that provide for a systematic approach to uncovering choices, to generating a shared view of consensus and divergence, and for making judgements and choices in model development

Methods for a rapid systematic review and meta-analysis in evaluating selective serotonin reuptake inhibitors for premature ejaculation

The aim of this study was to evaluate a rapid systematic review method in which randomised controlled trial (RCT) data was extracted from existing reviews and subsequent RCTs. The method enabled: identification of RCTs not included by existing reviews; cross-checking RCT data for consistency where there was more than one review; double data extraction due to time saved by extracting data from existing reviews; correction of data synthesis errors in existing reviews; and pooling data across all RCTs to produce contemporary effect estimates. When subsequently compared to extracting data directly from all RCT original publications, the findings and conclusions concurred

Meta-review of the effectiveness of computerised CBT in treating depression

<p>Abstract</p> <p>Background</p> <p>Several computerised cognitive behaviour therapy (cCBT) packages are now available to treat mild to moderate depression with or without anxiety. These have been usually been reviewed alongside cCBT for a wide range of psychological problems. Here, we single out the results of these reviews for the most common mental disorder, mild to moderate depression. The aim of this paper is to evaluate the quality of existing reviews and to enable reliable comparisons of alternative computer packages for the same patient group.</p> <p>Methods</p> <p>A thorough search and analysis of reviews of efficacy of cCBT published between 1999 and February 2011.</p> <p>Results</p> <p>The search yielded twelve systematic reviews from ten studies covering depression. Their methodology is appraised and selected findings are presented here.</p> <p>Conclusions</p> <p>The meta-review supports the efficacy of cCBT for treatment of depression; however there is limited information on different approaches, whose relative cost-effectiveness remains to be demonstrated. Suggestions are made for future studies in the field.</p

Health-related quality-of-life of coal-based sponge iron plant workers in Barjora, India: a cross-sectional study

OBJECTIVES: During the last decade, coal-based sponge iron plants, a highly polluted industry, have grown rapidly in Barjora, India. Understanding their workers’ perception of health is essential in people-centered healthcare. The aim of the study was to assess their health-related quality-of-life (HRQoL), and to determine factors that independently predict their HRQoL. DESIGN: Cross-sectional study. SETTING: Coal-based sponge iron plants in Barjora, India. PARTICIPANTS: 258 coal-based sponge iron plant workers. PRIMARY OUTCOME MEASURE: HRQoL was measured using the EuroQol-5D-5L. RESULTS: The response rate was 100%. Participants with problems in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 23.3%, 5.1%, 10.9%, 39.5% and 45.5%, respectively. 36.8% of participants reported health state 11111 (no problem in any EQ-5D dimension). The mean visual analogue scale (EQ-VAS) was 69.8 (18.5 SD). The odds of mobility problems decreased with age (OR 0.95, 95% CI 0.91 to 0.99, p=0.016), were lower in participants with presence/history of any respiratory disease (0.27, 0.13 to 0.55, p<0.001), scheduled caste/scheduled tribe/other backward class workers (0.44, 0.22 to 0.89, p=0.021), manual workers (0.40, 0.16 to 0.99, p=0.047) and non-smokers (2.63, 1.27 to 5.46, p=0.009). The odds of pain/discomfort and anxiety/depression were lower in participants with any respiratory disease (0.44, 0.24 to 0.79, p=0.006; and 0.52, 0.29 to 0.92, p=0.026, respectively). The EQ-VAS was worse in manual participants (coefficient −6.91, 95% CI −12.40 to −1.41, p=0.014), with any respiratory disease (−8.13, −13.12 to −3.13, p=0.002), alcohol drinkers (−4.81, −9.47 to −0.15, p=0.043), literates (7.70, 0.97 to 14.43, p=0.025) and Hindus (13.41, 2.62 to 24.20, p=0.015). CONCLUSIONS: Many coal-based sponge iron plant workers in Barjora have problems in their HRQoL, and the predictors of different aspects of HRQoL were identified. The study findings could be taken into consideration in future interventional studies aimed at improving the HRQoL of these workers

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

Psychological and psychosocial interventions for cannabis cessation in adults: a systematic review short report

Background: Cannabis is the most commonly used illicit drug worldwide. Cannabis dependence is a recognised psychiatric diagnosis, often diagnosed via the Diagnostic and Statistical Manual of Mental Disorders criteria and the International Classification of Diseases, 10th Revision. Cannabis use is associated with an increased risk of medical and psychological problems. This systematic review evaluates the use of a wide variety of psychological and psychosocial interventions, such as motivational interviewing (MI), cognitive–behavioural therapy (CBT) and contingency management. Objective: To systematically review the clinical effectiveness of psychological and psychosocial interventions for cannabis cessation in adults who use cannabis regularly. Data sources: Studies were identified via searches of 11 databases [MEDLINE, EMBASE, Cochrane Controlled Trials Register, Health Technology Assessment (HTA) database, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, NHS Economic Evaluation Database, PsycINFO, Web of Science Conference Proceedings Citation Index, ClinicalTrials.gov and metaRegister of Current Controlled Trials] from inception to February 2014, searching of existing reviews and reference tracking. Methods: Randomised controlled trials (RCTs) assessing psychological or psychosocial interventions in a community setting were eligible. Risk of bias was assessed using adapted Cochrane criteria and narrative synthesis was undertaken. Outcomes included change in cannabis use, severity of cannabis dependence, motivation to change and intervention adherence. Results: The review included 33 RCTs conducted in various countries (mostly the USA and Australia). General population studies: 26 studies assessed the general population of cannabis users. Across six studies, CBT (4–14 sessions) significantly improved outcomes (cannabis use, severity of dependence, cannabis problems) compared with wait list post treatment, maintained at 9 months in the one study with later follow-up. Studies of briefer MI or motivational enhancement therapy (MET) (one or two sessions) gave mixed results, with some improvements over wait list, while some comparisons were not significant. Four studies comparing CBT (6–14 sessions) with MI/MET (1–4 sessions) also gave mixed results: longer courses of CBT provided some improvements over MI. In one small study, supportive–expressive dynamic psychotherapy (16 sessions) gave significant improvements over one-session MI. Courses of other types of therapy (social support group, case management) gave similar improvements to CBT based on limited data. Limited data indicated that telephone- or internet-based interventions might be effective. Contingency management (vouchers for abstinence) gave promising results in the short term; however, at later follow-ups, vouchers in combination with CBT gave better results than vouchers or CBT alone. Psychiatric population studies: seven studies assessed psychiatric populations (schizophrenia, psychosis, bipolar disorder or major depression). CBT appeared to have little effect over treatment as usual (TAU) based on four small studies with design limitations (both groups received TAU and patients were referred). Other studies reported no significant difference between types of 10-session therapy. Limitations: Included studies were heterogeneous, covering a wide range of interventions, comparators, populations and outcomes. The majority were considered at high risk of bias. Effect sizes were reported in different formats across studies and outcomes. Conclusions: Based on the available evidence, courses of CBT and (to a lesser extent) one or two sessions of MI improved outcomes in a self-selected population of cannabis users. There was some evidence that contingency management enhanced long-term outcomes in combination with CBT. Results of CBT for cannabis cessation in psychiatric populations were less promising, but may have been affected by provision of TAU in both groups and the referred populations. Future research should focus on the number of CBT/MI sessions required and potential clinical effectiveness and cost-effectiveness of shorter interventions. CBT plus contingency management and mutual aid therapies warrant further study. Studies should consider potential effects of recruitment methods and include inactive control groups and long-term follow-up. TAU arms in psychiatric population studies should aim not to confound the study intervention. Study registration: This study is registered as PROSPERO CRD42014008952. Funding: The National Institute for Health Research HTA programme

The type and impact of Evidence Review Group (ERG) exploratory analyses in the NICE Single Technology Appraisal (STA) process

Background: As part of the UK National Institute for Health and Care Excellence (NICE) single technology appraisal process, independent evidence review groups (ERGs) critically appraise a company's submission relating to a specific technology and indication. Objectives: To explore the type of additional exploratory analyses conducted by ERGs and their impact on the recommendations made by NICE. Methods: The 100 most recently completed single technology appraisals with published guidance were selected for inclusion. A content analysis of relevant documents was undertaken to identify and extract relevant data, and narrative synthesis was used to rationalize and present these data. Results: The types of exploratory analysis conducted in relation to companies' models were fixing errors, addressing violations, addressing matters of judgment, and the provision of a new, ERG-preferred base case. Ninety-three of the 100 ERG reports contained at least one of these analyses. The most frequently reported type of analysis in these 93 ERG reports related to the category Matters of judgment, which was reported in 83 reports (89%). At least one of the exploratory analyses conducted and reported by an ERG is mentioned in 97% of NICE appraisal consultation documents and 94% of NICE final appraisal determinations, and had a clear influence on recommendations in 72% of appraisal consultation documents and 47% of final appraisal determinations. Conclusions: These results suggest that the additional analyses undertaken by ERGs in the appraisal of company submissions are highly influential in the policy-making and decision-making process