Hazel Squires

Systematic review of the efficacy of cilostazol, naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication

A systematic review and network meta‐analysis was undertaken to consider the evidence for the efficacy and tolerability of placebo, cilostazol, naftidrofuryl oxalate and pentoxifylline in patients with intermittent claudication due to peripheral arterial disease (PAD).

A Systematic Review and Economic Evaluation of Cilostazol, Naftidrofuryl Oxalate, Pentoxifylline and Inositol Nicotinate for the Treatment of Intermittent Claudication in People with Peripheral Arterial Disease

BACKGROUND Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the legs and arms. It is estimated to affect around 4.5% of people aged between 55 and 74 years within the UK. The most common symptom of PAD is intermittent claudication (IC), characterised by pain in the legs on walking that is relieved with rest. OBJECTIVE To assess the effectiveness and cost-effectiveness of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a period of conventional management. DATA SOURCE Electronic bibliographic databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings Citation Index, BIOSIS Previews). REVIEW METHODS Effectiveness outcomes sought were maximal walking distance (MWD), pain-free walking distance (PFWD), ankle-brachial pressure index, cardiovascular events, mortality, adverse events (AEs) and health-related quality of life (HRQoL). A narrative synthesis was provided for all outcomes and a network meta-analysis was undertaken for the walking distance outcomes. A Markov model was developed to assess the relative cost-effectiveness of the interventions from a NHS perspective over a lifetime. The model has three states: vasoactive drug treatment, no vasoactive drug treatment and death. Each 1-week cycle, patients may continue with the drug, discontinue the drug or die. Regression analysis was undertaken to model the relationship between MWD and utility so that a cost per quality-adjusted life-year (QALY) outcome measure could be presented. Univariate and probabilistic sensitivity analyses were undertaken. All costs and outcomes were discounted at 3.5%. RESULTS Twenty-six randomised controlled trials were identified that met the inclusion criteria for the clinical effectiveness review. There was evidence that walking distance outcomes were significantly improved by both cilostazol and naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to 0.762, respectively. It was not possible to include inositol nicotinate within the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however, the shorter-term data did not suggest a significant effect. AEs were minor for all drugs and included headaches and gastrointestinal difficulties. The incidence of serious adverse events (SAEs), including cardiovascular events and mortality, was not increased by the vasoactive drugs compared with placebo; however, most studies had a relatively short follow-up time to address this outcome. HRQoL data were limited. Two studies of limited quality were identified within the review of cost-effectiveness. The de novo model developed suggests that naftidrofuryl oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of around £6070 compared with no vasoactive drug. This result is reasonably robust to changes within the key model assumptions. Inositol nicotinate was not included within the main analysis owing to lack of data. However, it is unlikely to be considered to be cost-effective due to its high acquisition cost (£900 vs £100-500 per year for the other drugs). CONCLUSIONS Naftidrofuryl oxalate and cilostazol both appear to be effective treatments for this patient population, with minimal SAEs. However, naftidrofuryl oxalate is the only treatment that is likely to be considered cost-effective. The long-term effectiveness is uncertain and hence a trial comparing cilostazol, naftidrofuryl oxalate and placebo beyond 24 weeks would be beneficial. Outcomes associated with naftidrofuryl oxalate could also be compared with those associated with supervised exercise programmes and angioplasty.

Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta‐analysis

Aim  Antioxidants, such as vitamin A, C and E, selenium and β‐carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population.

Routine antenatal anti-D prophylaxis in women who are Rh(D) negative: meta-analyses adjusted for differences in study design and quality.

Background To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen adopted. Methods Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects meta-regression analysis. Results In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95% CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I 2 = 19%). However, this naïve analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95% CI 0.17, 0.56), with no evidence of heterogeneity (I 2 = 0%). A meta-regression analysis was performed, which used the data available from the ten anti-D prophylaxis studies to inform us about the relative effectiveness of three licensed treatments. This gave an 83% probability that a dose of 1250 IU at 28 and 34 weeks is most effective and a 76% probability that a single dose of 1500 IU at 28–30 weeks is least effective. Conclusion There is strong evidence for the effectiveness of routine antenatal anti-D prophylaxis for prevention of sensitisation, in support of the policy of offering routine prophylaxis to all non-sensitised pregnant Rhesus negative women. All three licensed dose regimens are expected to be effective.

Development of a Transparent Interactive Decision Interrogator to Facilitate the Decision-Making Process in Health Care

Background Decisions about the use of new technologies in health care are often based on complex economic models. Decision makers frequently make informal judgments about evidence, uncertainty, and the assumptions that underpin these models. Objectives Transparent interactive decision interrogator (TIDI) facilitates more formal critique of decision models by decision makers such as members of appraisal committees of the National Institute for Health and Clinical Excellence in the UK. By allowing them to run advanced statistical models under different scenarios in real time, TIDI can make the decision process more efficient and transparent, while avoiding limitations on pre-prepared analysis. Methods TIDI, programmed in Visual Basic for applications within Excel, provides an interface for controlling all components of a decision model developed in the appropriate software (e.g., meta-analysis in WinBUGS and the decision model in R) by linking software packages using RExcel and R2WinBUGS. TIDIs graphical controls allow the user to modify assumptions and to run the decision model, and results are returned to an Excel spreadsheet. A tool displaying tornado plots helps to evaluate the influence of individual parameters on the model outcomes, and an interactive meta-analysis module allows the user to select any combination of available studies, explore the impact of bias adjustment, and view results using forest plots. We demonstrate TIDI using an example of a decision model in antenatal care. Conclusion Use of TIDI during the NICE appraisal of tumor necrosis factor-alpha inhibitors (in psoriatic arthritis) successfully demonstrated its ability to facilitate critiques of the decision models by decision makers.

Views of contraceptive service delivery to young people in the UK: a systematic review and thematic synthesis

Background and methodology Despite widespread availability of contraceptives and increasing service provision in the UK, rates of teenage pregnancy remain a concern. It has been suggested that young people face particular obstacles in accessing services, leading to a need for specialist provision. This systematic review examined the literature reporting views of service providers and young people. Data were synthesised in order to develop key themes to inform the development of contraceptive services for this population. Results A total of 59 papers reporting studies carried out within the UK were included. Forty-five of these provided qualitative or mixed method data and 14 reported survey findings. Seven key themes were identified: perceptions of services; accessibility; embarrassment; anonymity and confidentiality; the clinic environment; the consultation; and service organisation. Conclusions This review suggests that the most significant concern for young people is the preservation of anonymity and confidentiality. There seems to be a need for young people to be given greater assurances about this, with process and environmental changes suggested. The fear of staff being critical or unfriendly also presents a considerable obstacle to some young people. Issues of service accessibility – such as convenience of location and opening hours – are also highlighted, with lifestyle factors and restrictions on where under-18s can go suggested as important aspects. The review suggests that varying preferences among young people with regard to which service to access requires choice to be preserved and, where possible, extended. This requires services to work effectively together to consider provision across a locality.

Cost-effectiveness of interventions to return employees to work following long-term sickness absence due to musculoskeletal disorders

BACKGROUND Sickness absence costs the UK economy around £20 billion per year. This study aims to assess the cost-effectiveness of interventions to return employees with musculoskeletal disorders to work, one of the major causes of long-term sickness absence, using a mathematical model. METHODS A Markov model was developed to assess the cost-effectiveness of three interventions: a workplace intervention; a physical activity and education intervention and a physical activity, education and workplace visit intervention. Extensive sensitivity analyses were undertaken to assess the impact of uncertainties upon the model results. RESULTS All interventions assessed are estimated to have a cost per quality-adjusted life year gained below £3000 compared with usual care within the UK from a National Health Service (NHS) or societal perspective. Moreover, any intervention which returns at least an additional 3% of employees to work and costs less than an additional £3000 per employee, is likely to be considered economically attractive compared with usual care, relative to other interventions routinely funded by the NHS. CONCLUSIONS This is the first economic evaluation in this area which extrapolates data beyond trial follow-up and synthesizes evidence from numerous sources. This sort of modelling approach should be considered for informing other public health policy decisions.

Systematic review and narrative synthesis of the effectiveness of contraceptive service interventions for young people, delivered in health care settings

A systematic review and narrative synthesis to determine the effectiveness of contraception service interventions for young people delivered in health care premises was undertaken. We searched 12 key health and medical databases, reference lists of included papers and systematic reviews and cited reference searches on included articles. All retrieved literature was screened at title and abstract levels, and relevant articles were taken through to full paper appraisal. Data relating to study design, outcomes and quality were extracted by one reviewer and independently checked by a second reviewer. We included interventions that consisted of contraceptive service provision for young people, and also interventions to encourage young people to use existing contraceptive services. The searches identified 23 studies that met the inclusion criteria. The papers focused on: new adolescent services, outreach to existing services, advanced provision of emergency contraception, condom/contraceptive provision and advice and repeat pregnancy prevention. The literature in general is not well developed in terms of good quality effectiveness studies and key outcome measures. However, it is possible to make recommendations in terms of outreach versus targeted young peoples services in health care settings, advanced provision of emergency contraception and long-acting reversible contraception to prevent repeat adolescent pregnancy.

A Framework for Developing the Structure of Public Health Economic Models

BACKGROUND A conceptual modeling framework is a methodology that assists modelers through the process of developing a model structure. Public health interventions tend to operate in dynamically complex systems. Modeling public health interventions requires broader considerations than clinical ones. Inappropriately simple models may lead to poor validity and credibility, resulting in suboptimal allocation of resources. OBJECTIVE This article presents the first conceptual modeling framework for public health economic evaluation. METHODS The framework presented here was informed by literature reviews of the key challenges in public health economic modeling and existing conceptual modeling frameworks; qualitative research to understand the experiences of modelers when developing public health economic models; and piloting a draft version of the framework. RESULTS The conceptual modeling framework comprises four key principles of good practice and a proposed methodology. The key principles are that 1) a systems approach to modeling should be taken; 2) a documented understanding of the problem is imperative before and alongside developing and justifying the model structure; 3) strong communication with stakeholders and members of the team throughout model development is essential; and 4) a systematic consideration of the determinants of health is central to identifying the key impacts of public health interventions. The methodology consists of four phases: phase A, aligning the framework with the decision-making process; phase B, identifying relevant stakeholders; phase C, understanding the problem; and phase D, developing and justifying the model structure. Key areas for further research involve evaluation of the framework in diverse case studies and the development of methods for modeling individual and social behavior. CONCLUSIONS This approach could improve the quality of Public Health economic models, supporting efficient allocation of scarce resources.

Modelling the economics of type 2 diabetes mellitus prevention: a literature review of methods.

Our objective was to review modelling methods for type 2 diabetes mellitus prevention cost-effectiveness studies. The review was conducted to inform the design of a policy analysis model capable of assisting resource allocation decisions across a spectrum of prevention strategies. We identified recent systematic reviews of economic evaluations in diabetes prevention and management of obesity. We extracted studies from two existing systematic reviews of economic evaluations for the prevention of diabetes. We extracted studies evaluating interventions in a non-diabetic population with type 2 diabetes as a modelled outcome, from two systematic reviews of obesity intervention economic evaluations. Databases were searched for studies published between 2008 and 2013. For each study, we reviewed details of the model type, structure, and methods for predicting diabetes and cardiovascular disease. Our review identified 46 articles and found variation in modelling approaches for cost-effectiveness evaluations for the prevention of type 2 diabetes. Investigation of the variables used to estimate the risk of type 2 diabetes suggested that impaired glucose regulation, and body mass index were used as the primary risk factors for type 2 diabetes. A minority of cost-effectiveness models for diabetes prevention accounted for the multivariate impacts of interventions on risk factors for type 2 diabetes. Twenty-eight cost-effectiveness models included cardiovascular events in addition to type 2 diabetes. Few cost-effectiveness models have flexibility to evaluate different intervention types. We conclude that to compare a range of prevention interventions it is necessary to incorporate multiple risk factors for diabetes, diabetes-related complications and obesity-related co-morbidity outcomes.