How methodological frameworks are being developed: evidence from a scoping review

Background: Although the benefits of using methodological frameworks are increasingly recognised, to date, there is no formal definition of what constitutes a ‘methodological framework’, nor is there any published guidance on how to develop one. For the purposes of this study we have defined a methodological framework as a structured guide to completing a process or procedure. This study’s aims are to: (a) map the existing landscape on the use of methodological frameworks; (b) identify approaches used for the development of methodological frameworks and terminology used; and (c) provide suggestions for developing future methodological frameworks. We took a broad view and did not limit our study to methodological frameworks in research and academia. Methods: A scoping review was conducted, drawing on Arksey and O’Malley’s methods and more recent guidance. We systematically searched two major electronic databases (MEDLINE and Web of Science), as well as grey literature sources and the reference lists and citations of all relevant papers. Study characteristics and approaches used for development of methodological frameworks were extracted from included studies. Descriptive analysis was conducted. Results: We included a total of 30 studies, representing a wide range of subject areas. The most commonly reported approach for developing a methodological framework was ‘Based on existing methods and guidelines’ (66.7%), followed by ‘Refined and validated’ (33.3%), ‘Experience and expertise’ (30.0%), ‘Literature review’ (26.7%), ‘Data synthesis and amalgamation’ (23.3%), ‘Data extraction’ (10.0%), ‘Iteratively developed’ (6.7%) and ‘Lab work results’ (3.3%). There was no consistent use of terminology; diverse terms for methodological framework were used across and, interchangeably, within studies. Conclusions: Although no formal guidance exists on how to develop a methodological framework, this scoping review found an overall consensus in approaches used, which can be broadly divided into three phases: (a) identifying data to inform the methodological framework; (b) developing the methodological framework; and (c) validating, testing and refining the methodological framework. Based on these phases, we provide suggestions to facilitate the development of future methodological frameworks

Conceptual models in health economic evaluation: a new role

Healthcare budgets are limited, and decisions must be made about which healthcare technologies should be funded from these limited budgets. Decision makers rely on clinical and cost-effectiveness evidence on which to base their decisions, the gold standard vehicle for this evidence is a clinical trial. Guidance exists for conducting economic evaluations alongside clinical trials using standard treatment arm-based comparisons to assess cost-effectiveness, however because of differences in the purposes of the clinical effectiveness and cost-effectiveness analyses this conventional treatment arm-based economic evaluation is often uncertain. Furthermore, economic evaluations focus on the final cost-effectiveness summary measure without consideration of what is driving this measure. There is scope for providing a more detailed understanding of the conventional cost-effectiveness results. Conceptual models are simplified versions of real-life systems in a visual format, illustrating how key components of the system are linked and interact within it. In the field of economic evaluation conceptual models are recommended for and used as a guide to establish the structure of decision analytic models, in other fields they are also used as a communication tool, to aid understanding of the system and to give direction to research. The aim of this thesis was to expand the role of conceptual models in economic evaluation. This thesis proposed a new role for conceptual models to provide additional understanding to decision makers, extending the conventional economic evaluation analysis beyond a treatment arm-based analysis. This role was demonstrated using two case studies as illustrative examples, aiming to show how the role could be applied. This thesis demonstrates the value of an additional conceptual model driven analysis to supplement the conventional treatment arm-based analysis, adding further insight into the trial mechanism and what is driving the economic evaluation results. The contribution of this thesis to the field of economic evaluation is twofold; a new role for conceptual models in economic evaluation and a methodological framework for developing conceptual models in this new role

Interventions in practice:reframing policy approaches to consumer behaviour

This report introduces a novel approach to sustainability policy— a practice perspective. We argue that social practices are a better target of intervention for sustainability policy than ‘behaviour’, ‘choice’ or technical innovation alone. Understanding the dynamics of practices offers us a window into transitions towards sustainability. We consume resources as part of the practices that make up everyday life—showering, doing the laundry, cooking or driving—what we might call inconspicuous or ordinary consumption. While we may have degrees of choice in how we perform these practices, access to resources (economic, social, cultural), norms of social interaction, as well as infrastructures and institutional organisation constrain our autonomy. Practices are social phenomena—their performance entails the reproduction of cultural meanings, socially learnt skills and common tools, technologies and products. This shift of perspective places practices, not individuals or infrastructures, at the centre stage of analysis. Taking practices as the unit of analysis moves policy beyond false alternatives—beyond individual or social, behaviour or infrastructure. A practice perspective re-frames the question from “How do we change individuals’ behaviours to be more sustainable?” to “How do we shift everyday practices to be more sustainable?” After all, ‘behaviours’ are largely individuals’ performances of social practices

Further evolution in the pharmaceutical sector : changes in the division of labour and the markets for technology

The pharmaceutical sector has undergone many changes, particularly in the past several decades. The purpose of this research was to ascertain the existence of further changes to the division of labour and changes in the markets for technology within the sector. This research was also undertaken to understand the specific issues that may be impacting the division of labour and the changes in the markets for technology including the role of finance and the role of a surplus of unexploited knowledge. The division of labour between large and small new firms was initially more pronounced as the fully integrated firms continued to develop, manufacture and market drugs while 'classical biotechnology' firms pursued an exploratory business model of supplying knowledge and early stage drug candidates to these fully integrated companies (McKelvey, 2008). However, firms are changing in this sector and changes may be evident that have not been discussed in the literature to date. A new type of firm is evident within this sector, the No Research Development Only (NRDO) firm, as well as changes in the existing firms. This has impacted markets for technology as changes are also apparent in the way in which firms exchange products and knowledge. A combined quantitative and qualitative study was used to answer the research questions. A random sample of 100 EU and US companies that own and develop drug products was generated. Descriptive statistics were gathered to form a database of information and case studies were compiled to provide in-depth data related to a sample of eight firms. The newly identified NRDO firms do not possess internal capabilities to discover their own products; surprising given the historically research intensive nature of the types of small firms that operate in this sector. There also appears to be changes in the markets for technology as large firms are selling drug candidates to these hitherto research-intensive discovery and development (DD) firms who are willing to in-license these drug candidates to bolster pipelines and financial valuations. Markets for knowledge in this sector have undoubtedly evolved and a more complex set of arrangements are evident. The roles of finance and a surplus of unexploited knowledge have played an important part in these changes as the sustained level of exploration in the sector has resulted in a greater number of exploitation opportunities. Overall there is evidence to support further evolution in the sector.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Health economic evaluation of lung cancer screening using a 2 diagnostic blood test : the Early detection of Cancer of the Lung 3 Scotland (ECLS)

Funding: Funding for the ECLS study was received from Oncimmune Ltd and the Scottish Government Health & Social Care Directorate of the Chief Scientist Office (CSO).Background: Diagnostic blood tests have the potential to identify lung cancer in people at high risk. We assessed the cost-effectiveness of a lung cancer screening intervention, using the EarlyCDT®-Lung Test (ECLS) with subsequent X-ray and low-dose chest CT scans (LDCT) for patients with a positive test result, compared to both usual care and LDCT screening for the target population. Methods: We conducted a model-based lifetime analysis from a UK NHS and personal social services perspective. We estimated incremental net monetary benefit (NMB) for the ECLS intervention compared to no screening and to LDCT screening. Results: The incremental NMB of ECLS intervention compared to no screening was GBP 33,179 (95% CI: −GBP 81,396, GBP 147,180) and GBP 140,609 (95% CI: -GBP 36,255, GBP 316,612), respectively, for a cost-effectiveness threshold of GBP 20,000 and GBP 30,000 per quality-adjusted life year. The same figures compared with LDCT screening were GBP 162,095 (95% CI: GBP 52,698, GBP 271,735) and GBP 52,185 (95% CI: −GBP 113,152, GBP 220,711). Conclusions: The ECLS intervention is the most cost-effective screening alternative, with the highest probability of being cost-effective, when compared to no screening or LDCT screening. This result may change with modifications of the parameters, suggesting that the three alternatives considered in the main analysis are potentially cost-effective.Peer reviewe

Health economic evaluation of lung cancer screening using a diagnostic blood test: the Early detection of Cancer of the Lung Scotland (ECLS)

Background: Diagnostic blood tests have the potential to identify lung cancer in people at high risk. We assessed the cost-effectiveness of a lung cancer screening intervention, using the Early CDT®-Lung Test (ECLS) with subsequent X-ray and low-dose chest CT scans (LDCT) for patients with a positive test result, compared to both usual care and LDCT screening for the target population. Methods: We conducted a model-based lifetime analysis from a UK NHS and personal social services perspective. We estimated incremental net monetary benefit (NMB) for the ECLS intervention compared to no screening and to LDCT screening. Results: The incremental NMB of ECLS intervention compared to no screening was GBP 33,179 (95% CI: −GBP 81,396, GBP 147,180) and GBP 140,609 (95% CI: -GBP 36,255, GBP 316,612), respectively, for a cost-effectiveness threshold of GBP 20,000 and GBP 30,000 per quality-adjusted life year. The same figures compared with LDCT screening were GBP 162,095 (95% CI: GBP 52,698, GBP 271,735) and GBP 52,185 (95% CI: −GBP 113,152, GBP 220,711). Conclusions: The ECLS intervention is the most cost-effective screening alternative, with the highest probability of being cost-effective, when compared to no screening or LDCT screening. This result may change with modifications of the parameters, suggesting that the three alternatives considered in the main analysis are potentially cost-effective

A protocol for the economic evaluation of the smoking Cessation in Pregnancy Incentives Trial III (CPIT III)

INTRODUCTION: Smoking results in an average 10-year loss of life, but smokers who permanently quit before age 40 can expect a near normal lifespan. Pregnancy poses a good opportunity to help women to stop; around 80% of women in the UK have a baby, most of whom are less than 40 years of age. Smoking prevalence during pregnancy is high: 17%-23% in the UK. Smoking during pregnancy causes low birth weight and increases the risk of premature birth. After birth, passive smoking is linked to sudden infant death syndrome, respiratory diseases and increased likelihood of taking up smoking. These risks impact the long-term health of the child with associated increase in health costs. Emerging evidence suggests that offering financial incentives to pregnant women to quit is highly cost effective.This protocol describes the economic evaluation of a multi-centre randomised controlled trial (Cessation in Pregnancy Incentives Trial III, CPIT III) designed to establish whether offering financial incentives, in addition to usual care, is effective and cost effective in helping pregnant women to quit. METHODS AND ANALYSIS: The economic evaluation will identify, measure and value resource use and outcomes from CPIT III, comparing participants randomised to either usual care or usual care plus up to £400 financial incentives. Within-trial and long-term analyses will be conducted from a National Health Service and Personal Social Services perspective; the outcome for both analyses will be quality adjusted life-years measured using EQ-5D-5L. Patient level data collected during the trial will be used for the within-trial analysis, with an additional outcome of cotinine validated quit rates at 34-38 weeks gestation and 6 months postpartum. The long-term model will be informed by data from the trial and published literature. ETHICS AND DISSEMINATION: TRIAL REGISTRATION NUMBER: ISRCTN15236311; Pre-results (https://doi.org/10.1186/ISRCTN15236311)

Financial incentives for quitting smoking in pregnancy : Are they cost-effective?

AIMS: To evaluate whether adding financial incentives to usual care is cost-effective in encouraging pregnant women to quit tobacco smoking, compared with usual care alone. DESIGN: Cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) from a health-care provider's perspective, embedded in the Smoking Cessation in Pregnancy Incentives Trial (CPIT III). Long-term analyses were conducted from the same perspective, using an existing Markov model over a life-time horizon. SETTING: Seven maternity smoking cessation sites in Scotland, England and Northern Ireland in the United Kingdom. PARTICIPANTS: In the short-term analysis, CPIT III participants were assessed: women 16 years or older, self-reporting as smokers, fewer than 24 weeks pregnant and English-speaking (n = 944). The same population was used for the life-time analysis, plus their infants. MEASUREMENTS: Costs included financial incentive vouchers and postage, cessation support and nicotine replacement therapy and neonatal stays. The outcome measure was a biochemically verified quit rate for the CEA and quality-adjusted life-years (QALYs) for CUA. Costs are presented in 2020 GBP sterling (£). Data for the life-time analysis came from the trial and were combined with data from published literature embedded in the model, reporting incremental cost per quitter and QALY. A 3.5% discount rate was applied. FINDINGS: The short-term incremental cost per quitter was £4400 and cost per QALY was £150 000. Results of sensitivity analyses confirmed these results. The long-term analysis combined costs and outcomes for mother and infants; results showed a cost saving of £37 [95% confidence interval (CI]) = £35-106] and increase in QALYs of 0.171 (95% CI = 0.124-0.229). These findings indicate that, over a life-time, financial incentives are cost-saving and improve health outcomes. CONCLUSIONS: In the United Kingdom, offering up to £400 financial incentives, in addition to usual care, to support pregnant women to stop smoking appears to be highly cost-effective over a life-time for mother and infants

Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD: A Randomized Clinical Trial

Importance: Chronic obstructive pulmonary disease (COPD) is a major global health issue and theophylline is used extensively. Preclinical investigations have demonstrated that low plasma concentrations (1-5 mg/L) of theophylline enhance antiinflammatory effects of corticosteroids in COPD.  Objective: To investigate the effectiveness of adding low-dose theophylline to inhaled corticosteroids in COPD.  Design, Setting, and Participants: The TWICS (theophylline with inhaled corticosteroids) trial was a pragmatic, double-blind, placebo-controlled, randomized clinical trial that enrolled patients with COPD between February 6, 2014, and August 31, 2016. Final follow-up ended on August 31, 2017. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid. This study included 1578 participants in 121 UK primary and secondary care sites.  Interventions: Participants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status) (n = 791) or placebo (n = 787).  Main Outcomes and Measures: The number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period.  Results: Of the 1567 participants analyzed, mean (SD) age was 68.4 (8.4) years and 54% (843) were men. Data for evaluation of the primary outcome were available for 1536 participants (98%) (772 in the theophylline group; 764 in the placebo group). In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, −0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08). Serious adverse events in the theophylline and placebo groups included cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%).  Conclusions and Relevance: Among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number COPD exacerbations over a 1-year period. The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations