Title: How do smoking cessation medicines compare with respect to their neuropsychiatric safety: a systematic review, network meta-analysis and cost effectiveness analysis.
Funder: Department of Health and Social Care

Abstract: Design: This is an evidence synthesis study and will include systematic reviews and network meta-analyses (NMAs) of the safety and effectiveness of the pharmacologic interventions for smoking cessation in addition to economic decision modelling. Strategy for reviewing the literature: Details of our search strategy are provided in Section 12 of the Detailed Project Description. We will search a range of databases and manually search the reference lists of relevant research articles and previous reviews and communicate with authors to identify unpublished information. We will also record information on the risk of bias for each trial; the Cochrane tool for assessing the risk of bias will be used (see Section 15) (46). Target population: All adult smokers who are seeking to quit smoking using prescribed smoking cessation therapies in NHS and primary care settings in the UK. This includes adult smokers accessing local authority stop smoking services. Health Technologies being assessed: These will include varenicline, bupropion, nicotine replacement therapy as monotherapy and in combination treatment (i.e. varenicline combined with NRT, varenicline combined with bupropion and bupropion compared with NRT). For NRT, combinations of different formulations given concurrently, for example patch and gum, will also be assessed. Different dosages of treatments will also be examined. Measurement of Costs and Outcomes: We will also update a previously reported economic model, created by the University of Sheffield, which is based on the Benefits of Smoking Cessation on Outcomes (BENESCO model), to assess cost-effectiveness of treatments for smoking cessation (13), and adapt it to incorporate adverse effects of treatments. A UK NHS perspective will be taken, with future costs and benefits discounted at a rate of 3.5% per year. Sample Size: Not applicable Project timetables including recruitment rate: The total project time is 26 months. Total time to conduct the systematic reviews including the retrieval of economic analyses, data extraction and preparation will be 14 months. Statistical analyses for the NMAs and the health economic analyses will be carried out in the final 12 months, together with writing of the project report and dissemination of the project’s findings to the general public, healthcare practitioners and clinicians, academics (via peer reviewed publications and presentations at conferences), industry and policy makers including the MHRA and NICE. We will involve patients and the public throughout the project via members of the UK Centre for Alcohol and Tobacco Studies (UKCTAS) Smokers’ Panel and the Elizabeth Blackwell Institute’s Public Advisory Group. Expertise in team: We are a multidisciplinary team of epidemiologists, biostatisticians, public health clinicians, health economists and biological psychologists based within the University Of Bristol- School Of Social and Community Medicine, the Centre for Public Health, the Tobacco and Alcohol Research Group, the Centre for Research Synthesis and Decision Making (CReSyDa) and the University of Sheffield- School of Health and Related Research (ScHARR). We have a track record of collaborating and publishing research of the highest quality and impact. Please see Section 21 for a detailed description of the team members, their contributions and responsibilities and how this project will fit within the core aims of each of the centres.

Lay abstract: Background to the research Cigarette smoking is one of the main causes of early death in the UK and worldwide. Each year, over 100,000 people die in the UK from smoking related diseases. National guidance published in 2008 recommends the use of three medicines, varenicline (Champix), bupropion (Zyban) and nicotine replacement therapy to help people quit smoking. However, since that guidance was first published there have been concerns about the safety of some of these medicines, especially varenicline. Some reports have suggested that smokers prescribed varenicline might be more likely than smokers prescribed other quit smoking medicines to experience mental health problems such as depression and suicidal thoughts. As a result, organisations which regulate medicines in the UK and the US have issued warnings about the safety of varenicline. Aims of the research In this study we will combine information from previous clinical trials to assess which quit smoking medicine is the safest and most effective. Design and Methods used: We will use special techniques which will allow us to make comparisons across all pairs of quit smoking medicines for example varenicline compared with bupropion, bupropion compared with NRT and varenicline compared with NRT; this improves on previous reviews which have mostly compared a particular quit smoking medicine with placebo (i.e. a sugar pill) when assessing safety and effectiveness of these medicines. We will also improve a previously published economic model by including side effects; this improved model will help us to determine which quit smoking medicine offers the best value for money for the NHS. We will determine whether this differs in different groups of smokers, including heavy smokers (i.e. people who smoke >20 cigarettes per day), people with mental illnesses and people with lung or heart disease. Patient and Public Involvement Members of a Smokers’ panel identified this research topic as high priority. These members also helped us in preparing this proposal and provided comments to improve this lay summary. We plan to involve members of this panel and members of the Public Advisory Group of the Elizabeth Blackwell Institute throughout the project. Dissemination This project’s findings will be shared with the general public, healthcare practitioners and clinicians, local authority smoking cessation teams, academics (via peer reviewed publications and presentations at conferences), industry and policy makers including the Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Health and Care Excellence (NICE). This research will allow smokers who want to quit and their healthcare professionals (GPs, smoking cessation advisors) to make informed decisions about the risks and benefits of quit smoking medicines using the most up to date evidence available. Information on which quit smoking medicine is the best value for money will be of value to policy makers in the UK and people who commission services in the NHS.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;RESPIRATORY;STROKE