Employing early decision analytic modelling to inform economic evaluation in health care: theory & practice

Decision analytic modelling (DAM) is a mathematical technique which is used to structure and synthesise evidence in order to inform decision making, given uncertainty. Decision models are an ideal tool for undertaking economic evaluations as they enable a wide range of data on costs and effects to be synthesised within the model in order to derive cost-effectiveness outcomes. The iterative framework for economic appraisal has been proposed as good practice for undertaking economic evaluations (1), and DAM plays a key role within this framework. In particular there is a role for early stage DAM prior to primary research, to provide an indication of the potential cost-effectiveness of a new health technology (2) given current evidence, and the use of value of information (VOI) techniques to help inform further research priority setting. In practice, support and funding for early stage DAM and full exploitation of VOI techniques is rare. The aim of this thesis is to examine the role for early decision analytic modelling in informing research priorities and the design of future studies in a health care setting. This thesis explores the feasibility, merits and drawbacks of undertaking early DAM and considers potential reasons as to why it has not been more widely implemented. This thesis demonstrates the value and importance of early DAM; in both an ‘ideal’ setting and also in a less desirable, time-constrained setting. Applying early DAM and VOI techniques enables researchers to provide relevant conclusions and recommendations to decision makers, who can make informed decisions as to whether a new intervention should be adopted (or rejected), or whether further information is required to help make the decision; as opposed to making decisions based on subjective reasoning. There is considerable merit with employing early DAM for health care research, such as reduced uncertainty, reduction of costs and efficiency gains, however, some drawbacks exist in terms of whether it is always viable to fully exploit VOI analyses, which may hinder widespread support both inside and out-with the health economics community

Effect of offering different levels of support and free nicotine replacement therapy via an English national telephone quitline: randomised controlled trial

Objective To compare the effects of free nicotine replacement therapy or proactive telephone counselling in addition to standard smoking cessation support offered through a telephone quitline

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)

Framework for the development and evaluation of complex interventions: gap analysis, workshop and consultation-informed update.

BACKGROUND: The Medical Research Council published the second edition of its framework in 2006 on developing and evaluating complex interventions. Since then, there have been considerable developments in the field of complex intervention research. The objective of this project was to update the framework in the light of these developments. The framework aims to help research teams prioritise research questions and design, and conduct research with an appropriate choice of methods, rather than to provide detailed guidance on the use of specific methods. METHODS: There were four stages to the update: (1) gap analysis to identify developments in the methods and practice since the previous framework was published; (2) an expert workshop of 36 participants to discuss the topics identified in the gap analysis; (3) an open consultation process to seek comments on a first draft of the new framework; and (4) findings from the previous stages were used to redraft the framework, and final expert review was obtained. The process was overseen by a Scientific Advisory Group representing the range of relevant National Institute for Health Research and Medical Research Council research investments. RESULTS: Key changes to the previous framework include (1) an updated definition of complex interventions, highlighting the dynamic relationship between the intervention and its context; (2) an emphasis on the use of diverse research perspectives: efficacy, effectiveness, theory-based and systems perspectives; (3) a focus on the usefulness of evidence as the basis for determining research perspective and questions; (4) an increased focus on interventions developed outside research teams, for example changes in policy or health services delivery; and (5) the identification of six 'core elements' that should guide all phases of complex intervention research: consider context; develop, refine and test programme theory; engage stakeholders; identify key uncertainties; refine the intervention; and economic considerations. We divide the research process into four phases: development, feasibility, evaluation and implementation. For each phase we provide a concise summary of recent developments, key points to address and signposts to further reading. We also present case studies to illustrate the points being made throughout. LIMITATIONS: The framework aims to help research teams prioritise research questions and design and conduct research with an appropriate choice of methods, rather than to provide detailed guidance on the use of specific methods. In many of the areas of innovation that we highlight, such as the use of systems approaches, there are still only a few practical examples. We refer to more specific and detailed guidance where available and note where promising approaches require further development. CONCLUSIONS: This new framework incorporates developments in complex intervention research published since the previous edition was written in 2006. As well as taking account of established practice and recent refinements, we draw attention to new approaches and place greater emphasis on economic considerations in complex intervention research. We have introduced a new emphasis on the importance of context and the value of understanding interventions as 'events in systems' that produce effects through interactions with features of the contexts in which they are implemented. The framework adopts a pluralist approach, encouraging researchers and research funders to adopt diverse research perspectives and to select research questions and methods pragmatically, with the aim of providing evidence that is useful to decision-makers. FUTURE WORK: We call for further work to develop relevant methods and provide examples in practice. The use of this framework should be monitored and the move should be made to a more fluid resource in the future, for example a web-based format that can be frequently updated to incorporate new material and links to emerging resources. FUNDING: This project was jointly funded by the Medical Research Council (MRC) and the National Institute for Health Research (Department of Health and Social Care 73514)

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

Cervical ripening at home or in-hospital-prospective cohort study and process evaluation (CHOICE) study: a protocol.

IntroductionThe aim of the cervical ripening at home or in-hospital-prospective cohort study and process evaluation (CHOICE) study is to compare home versus in-hospital cervical ripening to determine whether home cervical ripening is safe (for the primary outcome of neonatal unit (NNU) admission), acceptable to women and cost-effective from the perspective of both women and the National Health Service (NHS).Methods and analysisWe will perform a prospective multicentre observational cohort study with an internal pilot phase. We will obtain data from electronic health records from at least 14 maternity units offering only in-hospital cervical ripening and 12 offering dinoprostone home cervical ripening. We will also conduct a cost-effectiveness analysis and a mixed methods study to evaluate processes and women/partner experiences. Our primary sample size is 8533 women with singleton pregnancies undergoing induction of labour (IOL) at 39+0 weeks' gestation or more. To achieve this and contextualise our findings, we will collect data relating to a cohort of approximately 41 000 women undergoing IOL after 37 weeks. We will use mixed effects logistic regression for the non-inferiority comparison of NNU admission and propensity score matched adjustment to control for treatment indication bias. The economic analysis will be undertaken from the perspective of the NHS and Personal Social Services (PSS) and the pregnant woman. It will include a within-study cost-effectiveness analysis and a lifetime cost-utility analysis to account for any long-term impacts of the cervical ripening strategies. Outcomes will be reported as incremental cost per NNU admission avoided and incremental cost per quality adjusted life year gained.Research ethics approval and disseminationCHOICE has been funded and approved by the National Institute of Healthcare Research Health Technology and Assessment, and the results will be disseminated via publication in peer-reviewed journals.Trial registration numberISRCTN32652461

Reprint of: 'A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance'

The UK Medical Research Council's widely used guidance for developing and evaluating complex interventions has been replaced by a new framework, commissioned jointly by the Medical Research Council and the National Institute for Health Research, which takes account of recent developments in theory and methods and the need to maximise the efficiency, use, and impact of research. Complex interventions are commonly used in the health and social care services, public health practice, and other areas of social and economic policy that have consequences for health. Such interventions are delivered and evaluated at different levels, from individual to societal levels. Examples include a new surgical procedure, the redesign of a healthcare programme, and a change in welfare policy. The UK Medical Research Council (MRC) published a framework for researchers and research funders on developing and evaluating complex interventions in 2000 and revised guidance in 2006 (Campbell et al., 2000; Craig et al., 2008; Craig et al., 2006). Although these documents continue to be widely used and are now accompanied by a range of more detailed guidance on specific aspects of the research process (Craig et al., 2012; Craig et al., 2018; Moore et al., 2015; Moore et al., 2021; O’Cathain et al., 2019), several important conceptual, methodological and theoretical developments have taken place since 2006. These developments have been included in a new framework commissioned by the National Institute of Health Research (NIHR) and the MRC (Skivington et al., 2021). The framework aims to help researchers work with other stakeholders to identify the key questions about complex interventions, and to design and conduct research with a diversity of perspectives and appropriate choice of methods

A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance

The UK Medical Research Council’s widely used guidance for developing and evaluating complex interventions has been replaced by a new framework, commissioned jointly by the Medical Research Council and the National Institute for Health Research, which takes account of recent developments in theory and methods and the need to maximise the efficiency, use, and impact of research

Eradicating hepatitis C:Are novel screening strategies for people who inject drugs cost-effective?

Background: In developed countries, people who inject drugs (PWID) have a high prevalence of hepatitis C virus (HCV), yet they are often under-diagnosed. The World Health Organization has set 2030 as a target year for HCV elimination. To meet this target, improving screening in convenient community settings in order to reach infected undiagnosed individuals is a priority. This study assesses the cost-effectiveness of alternative novel strategies for diagnosing HCV infection in PWID. Methods: A cost-effectiveness analysis was undertaken to compare HCV screening at needle exchange centres, substance misuse services and at community pharmacies, with the standard practice of detection during general practitioners’ consultations. A decision tree model was developed to assess the incremental cost per positive diagnosis, and a Markov model explored the net monetary benefit (NMB) and the cost per Quality Adjusted Life Years (QALYs) gained over a lifetime horizon. Results: Needle exchange services provided a 7.45-fold increase in detecting positive individuals and an incremental cost of £12,336 per QALY gained against current practice (NMB £163,827), making this the most cost-effective strategy over a lifetime horizon. Screening at substance misuse services and pharmacies was cost-effective only at a £30,000/QALY threshold. With a 24% discount to HCV treatment list prices, all three screening strategies become cost-effective at £20,000/QALY. Conclusions: Targeting PWID populations with screening at needle exchange services is a highly cost-effective strategy for reaching undiagnosed HCV patients. When applying realistic discounts to list prices of drug treatments, all three strategies were highly cost-effective from a UK NHS perspective. All of these strategies have the potential to make a cost-effective contribution to the eradication of HCV by 2030