Title: Improving effectiveness of nicotine replacement therapy for smoking cessation in pregnancy through better adherence and adequate dosing.
Funder: Department of Health and Social Care

Abstract: Aims, objectives and questions We aim to evaluate how the NHS can support pregnant smokers to effectively and safely use nicotine replacement therapy (NRT) for smoking cessation. We plan to develop a complex intervention to help pregnant quitters better titrate the nicotine from NRT to suit their needs and to assess whether this increases adherence to NRT, smoking cessation rates and cost effectiveness of NHS cessation support. Key research questions Workstream (WS1): Identifying intervention messages How can NRT be used safely in pregnancy? What are pregnant smokers concerns about NRT and how can health professionals respond? What are the barriers against and facilitators for integrating professionals responses into routine practice? WS2: Intervention feasibility of delivery, refinement and evaluation How can WS1messages be integrated into a complex intervention? How can delivery of this intervention to pregnant smokers be optimised? What is the most objective way to measure pregnant quitters adherence to NRT? Can health professionals be trained to deliver the complex intervention? WS3: Impact on adherence to NRT Does the intervention safely increase pregnant smokers adherence to NRT, demonstrating feasibility for improving smoking cessation rates? WS4: Impact on smoking cessation Is the intervention effective and cost effective for promoting smoking cessation amongst pregnant smokers who use Stop Smoking Service Support? Background and rationale Smoking in pregnancy is a massive cause of morbidity and mortality and stopping smoking reduces health inequalities. In the UK, 26% of pregnant women smoke and NRT is offered to all who seek support with stopping. Although NRT is effective outside of pregnancy, our systematic review shows this has only borderline efficacy in pregnancy; this lack of efficacy is explained by pregnant quitters poor adherence to NRT. Our qualitative work shows pregnant smokers who have been prescribed NRT have substantial safety concerns and so underuse this. We have also shown that pregnant smokers have accelerated nicotine metabolism and so quitters need more NRT to generate sufficiently high blood nicotine concentrations to control symptoms of tobacco withdrawal. This suggests that for NRT to help pregnant quitters stop, they need to use more NRT at higher doses than non-pregnant quitters ; four secondary analyses of data from our large NRT trial are consistent with this hypothesis. In four work streams (WS) we develop and test a combined behavioural and pharmacological complex intervention to improve NRT adherence and also cessation rates. Research Plan WS1: Key messages for behavioural intervention components are derived using reviews of NRT safety and of pregnant smokers concerns about nicotine; qualitative work with cessation advisors and pregnant smokers; PPI input and an expert group. WS2: A prototype intervention combining behavioural and pharmacological approaches will be developed and delivered to sequential cohorts of pregnant smokers (n=10) from whom we will seek feedback. Based on previous work, the pharmaceutical component will involve providing dual NRT - a longer acting NRT (e.g. patch) together with a shorter acting one (e.g. inhalator). We will investigate how to collect objective and complete NRT adherence data by comparing the amount of NRT used with usage reported by text message, phone and questionnaires, finalising outcome measurement for a trial. WS3: An RCT enrolling 200 pregnant smokers will test whether the intervention improves NRT adherence, monitoring the impact on nicotine exposure. WS4: In a full within-trial pilot we will assess the feasibility of training SSS staff in intervention delivery and of all other trial methods. The subsequent full trial will be a cluster-randomised, stepped-wedge RCT (sample size = 2550 pregnant quitters ) in which the intervention is introduced at a service-level into 25 SSS; the primary outcome will be smoking abstinence for at least 6 months. Economics: In WS 3, we will monitor costs involved in intervention delivery and, for WS 3 and WS 4 trials, using an economic model derived for a previous NIHR programme, we will model longer term cost effectiveness of the intervention from both maternal and infant perspectives. Projected outputs and dissemination As well as standard scientific and policy dissemination, rapid NHS dissemination is planned. Key outputs are an online training module and a face to face course in intervention delivery for health professionals; after the programme these will be immediately available to the NHS. Regionally, the East Midlands Academic Health Science Network is supportive and would consider providing support for face to face staff training to ensure a proven intervention is integrated into practice. NHS benefits We will aim for the intervention to replace aspects of behavioural support and not add to the time needed for support delivery. If effective, the intervention could increase NRT prescribing costs but modelling shows that these would need to be very high for the intervention to not prove very cost effective; mothers and infants could even benefit from substantially better health whilst the NHS makes cost-savings.

Lay abstract: Smoking is the biggest killer in the developed world. When pregnant women smoke, babies are more likely grow slowly in the womb and experience future health problems. Smokers children are more likely to smoke themselves, so stopping in pregnancy improves women s and infants health and ultimately reduces numbers of future adult smokers. Pregnant women are very motivated to stop smoking; many try but most fail or re-start after birth. The English NHS helps around 20,000 pregnant smokers each year; most are offered nicotine replacement therapy (NRT) which the NHS considers safer than smoking. NRT provides clean nicotine without cancer-causing chemicals; users feed nicotine urges without smoking and can stop for good, but most pregnant smokers who are given NRT don t use this regularly or for long enough for it to work. Although NRT contains only nicotine, many pregnant smokers have concerns about using it, which is why most use low NRT doses which do not control unpleasant withdrawal feelings. Another reason for low use of NRT in pregnancy is that pregnant women s bodies break down nicotine much faster and for pregnant smokers to avoid the unpleasant feelings that come from not having enough nicotine ( withdrawal ), they need higher doses of NRT than they would have done before pregnancy. Overall, pregnant smokers are more likely to stop using NRT and re-start smoking to help reduce withdrawal ; this means that NRT may not be helping them to stop as much as it could. We will develop support reinforced by text message which encourages pregnant smokers to use as much NRT as they need to control their withdrawal . With this support pregnant quitters will be offered a NRT patch to provide a steady nicotine dose and a rapid-acting NRT for short term dose top ups which women will learn to use when they need more nicotine. We will test whether we can train health professionals to support pregnant smokers using these methods. We want to help pregnant smokers make best use of NRT and stop smoking for good by: 1 Discovering from published work how NRT is best used in pregnancy and, by finding from pregnant smokers the information they need to address concerns about NRT 2 Using findings from the above work to design an intervention which addresses concerns and encourages pregnant smokers to use enough NRT for this to work. 3 Testing whether or not women who receive the intervention use more NRT 4 Testing whether or not the intervention, used within routine NHS stop smoking services, causes more pregnant smokers to stop smoking than current standard NHS support. If it works, this cheap intervention will be ready for immediate use and will probably save NHS money.

Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: RESPIRATORY;STROKE;CARDIOVASCULAR;CANCER AND NEOPLASMS;REPRODUCTIVE HEALTH AND CHILDBIRTH