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Study protocol for a randomised controlled trial of Allen Carr’s Easyway programme versus Lambeth and Southwark NHS service for smoking cessation.

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Manuscript ID Article Type:

Date Submitted by the Author:

Wood, Kerry; London South Bank University, Psychology Albery, Ian; London South Bank University, Department of Psychology Moss, Anthony ; London South Bank University, Psychology White, Sarah; St George's University of London, Division of Population Health Sciences and Education Frings, Daniel; London South Bank University, Division of Psychology Public health

Health services research, Smoking and tobacco, Global health PUBLIC HEALTH, Smoking, Randomised Controlled Trial

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Keywords:

15-Mar-2017

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Secondary Subject Heading:

Protocol

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Primary Subject Heading:

bmjopen-2017-016867

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Complete List of Authors:

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Kerry V. Wood1, Ian P. Albery1, Antony Moss1, Sarah White2, Daniel Frings1

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Division of Psychology, London South Bank University, 103 Borough Road, London SE1 0AA, UK.

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Population Health Research Institute, St Georges University of London, Cranmer Terrace, Tooting, London, SW17 ORE, UK.

Correspondence to Kerry V Wood via the above address or [email protected] or tel.: 020778155466.

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ABSTRACT Introduction: Smoking is a major cause of ill health and is associated with several diseases including cancer, coronary heart disease and stroke. Many psychological and pharmacological smoking cessation treatments are available and although they are undoubtedly the most cost-effective health intervention available, many people still fail to maintain cessation in the long-term. Recently NICE called for comparative studies to determine the short- and long-term effectiveness of Allen Carr's Easyway (ACE) method of stopping smoking. This study will compare the efficacy of the ACE programme and a 1-1 counselling service available via the NHS. Methods and analysis: A two-arm, parallel-group, double blinded, randomised controlled trial will be conducted with people who smoke tobacco cigarettes, aged 18 or over, are motivated to quit and live or work in Lambeth and Southwark. Exclusion criteria include mental health condition, pregnancy or respiratory disease such as chronic obstructive pulmonary disease or emphysema will be excluded. The primary treatment outcome is smoking cessation 24 weeks after treatment. Participants will be analysed on an intention to treat basis at the point of randomisation. Logistic regression will be used to estimate the effectiveness of the treatment condition upon smoking cessation at six months. The following covariates will be included: baseline quit efficacy (at inclusion), age (at inclusion), gender and baseline nicotine dependency. Ethics and Dissemination: Approval was granted by London – Fulham Research Ethics Committee (ref: 16/LO/1657). The study’s findings will be published in peer-reviewed journals and disseminated at national and international conferences. Trial Registration: ClinicalTrials.gov Identifier Number NCT02855255; ISRCTN registration number: ISRCTN23584477.

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STRENGTHS AND LIMITATIONS Strengths • This study adopted a Blinded Randomised Controlled Trial design • Chemical verification of quit success • Comparison of two common smoking cessation interventions Limitations • Our sample is geographically limited to Lambeth and Southwark boroughs of London • No ‘no treatment’ control

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INTRODUCTION Dependence on nicotine has long been a problem and although statistics from the World Health Organization (1) show that the prevalence of tobacco smoking is declining worldwide, there are still a significant number of people, 1.1 billion in 2015, who continue to smoke (1) Smoking is a major cause of ill health and is associated with several diseases including cancer, coronary heart disease, and stroke. In the UK alone in 2014, there were 9.6 million smokers, with 78,000 deaths attributed to smoking (2) Many smokers want to quit and often make several attempts to do so, but the majority fail due to both physiological and psychological factors (3). Over the years, researchers have sought to develop effective cessation treatments in an effort to provide education and support. Consequently, many psychological and pharmacological treatments are available to help smokers quit, and although these types of intervention are undoubtedly the most costeffective interventions available (4), many people fail to maintain smoking cessation in the longer term (5). In 2014, it was reported that 37% of smokers made an attempt to quit, however, only 19%, a little over half, were actually successful (6).

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It is important to understand the relative efficacies of various interventions designed to help people quit, and recently NICE called for comparative studies to determine the short- and long-term effectiveness of Allen Carr's Easyway method of stopping smoking. Whilst the Allen Carr's Easyway (ACE) to stop smoking programme is well-established and its efficacy has received some empirical support (see Dijkstra et al. [7]), there has not to date been a randomised control trial testing the efficacy of this programme.

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To test the efficacy of the ACE programs against existing provision, this study will compare the efficacy of two stop smoking interventions, amongst people living and working in the Lambeth and Southwark boroughs of London. Specifically, Allen Carr's Easyway to stop smoking programme and a 1-1 counselling service available via the NHS will be compared. Participants will be followed up at 4, 12 and 24 weeks post treatment. The primary treatment outcome measure is smoking cessation 24 weeks after treatment. Alongside the primary outcome (actual cessation), the research will also aim to evaluate the effect of each treatment on the following secondary outcomes: self-reported maintenance of smoking cessation, readiness to change, perceived efficacy/confidence in current and future quit success, perceived value of being nicotine free, life satisfaction and use of nicotine replacement therapy (NRT)/nicotine containing products. By comparing the ACE programme to a NHS delivered treatment program, an estimate of the relative effectiveness of ACE in comparison to the NHS service can be made. This will potentially inform future judgements about the use of this method by private and public health care providers. The findings will add to the evidence base around the use of the NHS stop smoking service and the Allen Carr’s Easyway method.

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METHODS/DESIGN Design A two-arm, parallel-group, double blinded1, randomised controlled trial. Treatment setting/site All intervention sessions for the NHS and ACE programmes will be delivered on the London South Bank University (LSBU) Southwark campus and the Allen Carr’s Easyway site in SW20. They begin in February 2017 and will run for eight months.

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Study population

People living and/or working in the Lambeth and Southwark boroughs of London, England, who smoke tobacco cigarettes and are motivated to quit. Inclusion and exclusion criteria

Participants will be eligible provided they are at least 18 years of age, are current smokers who intend to quit, live or work in Lambeth / Southwark areas and are prepared to be assigned randomly to one of two treatment conditions (NHS standard provision or ACE). Individuals who, on being asked at the point of recruitment would prefer an NHS provided treatment, are currently in another RCT or similar research project, disclose that they have a mental health condition, are pregnant or have a respiratory disease such as chronic obstructive pulmonary disease or emphysema will be excluded. Additionally, individuals who feel they are unable to reach the treatment location (London South Bank University’s Southwark Campus or SW20) for treatment and follow-up will also be excluded.

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Interventions

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Allen Carr’s Easyway programme. The ACE intervention involves a single group session with up to 25 attendees, led by a trained facilitator. The five to six-hour session broadly comprises elements of CBT and ends with a short hypnotherapy/relaxation exercise. Participants are encouraged to carry on smoking as normal right up until they attend the clinic and during the session are encouraged to smoke as normal during scheduled smoking breaks (around every 45-60 minutes). Participants are assisted in identifying positive expectancies they associate with smoking (e.g. pleasure, support, crutch, or other benefits) before working towards the conclusion that the belief that smoking provides these benefits is, in fact, erroneous and harmful. Participants also achieve a basic understanding of how the psychological and pharmacological mechanisms of nicotine addiction facilitate the maintenance of erroneous and problematic beliefs. These sessions end with a ‘ritual’ final cigarette followed by an approximately 20-minute period of hypnotherapy – a light

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relaxation exercise that reinforces the main points of the session. At the end of each session each participant is asked to make a written record of what it was about their life as a smoker that made them want to stop. Following each session, the clinical team will call, email, or SMS text the participant on day 1, and again at 3, 7, 10, 14, 21, 30, 45, 60, 75, and 90 days with a short courtesy message such as “Hope you’re well. Please don’t hesitate to get in touch if you have any questions at all”, “Hope all is well with you. Don’t forget we’re here if you have any questions”. NHS smoking cessation programme. The NHS intervention comprises the NHS stop smoking service offered at Guys and St Thomas NHS Foundation Trust. This constitutes a single session of around 30 minutes which combines motivational interviewing and CBT, followed by four follow-up sessions. The initial session involves informing the client about the treatment programme, assessing current smoking, readiness to quit and past quit attempts. Participants are then advised on the operation of nicotine dependence, the mechanics of withdrawal, and given advice on changing routine. The use, pros and cons of various NRTs are also outlined. A quit date is set, and the importance of complete abstinence discussed. Finally, a carbon monoxide test is administered, and explained. Before the session finishes, participants are assisted in identifying high risk situations in the coming week, and develop quit action plans. This treatment is combined with prescribed NRT of the patients’ choice. One, two and three weeks’ post quit date, shorter meetings (approximately 10 minutes) are arranged. These involve a progress check, a discussion around withdrawal symptoms and coping, a check on NRT supplies, a reflection on difficult situations encountered, a carbon monoxide test and planning for high risk situations in the coming week. The importance of abstinence is finally re-enforced. Four weeks after the quit date, an approximately 10minute meeting checks on progress, measures carbon monoxide, advises on continued use of medication, discusses craving and urges and difficult situations and finally reinforces the importance of complete abstinence.

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Top-ups and Resets. Both treatments contain as standard, options to reset/top up quit dates. The ACE provision includes the option for clients to ‘top-up’ their treatment in two further sessions. These second and third sessions broadly follow the same format (approximately 3.5 hours) but contain more interaction and a smaller group (up to 15 clients) and either be carried out face-to-face or online. They can take place up to three months from the initial session. The clinician will provide contact details through which these sessions can be arranged. Should these optional sessions be taken up by a participant then the use of a top-up, and the date will be recorded by the clinician on the participant schedule and the subsequent testing dates will be based on the reset date. The primary outcome will be counted from the reset date (e.g. prior cigarettes consumed up to that point will be disregarded). The NHS arm contains the option for participants to be given a chance to reset their quit date, at the discretion and suggestion of the clinician. Should a reset be offered, the use of a reset will be recorded, revised date will be recorded by the clinician on the participant schedule and the subsequent testing dates will be based on the

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reset date. The primary outcome will be counted from the reset date (e.g. prior cigarettes consumed up to that point will be disregarded). Outcomes Primary Outcome Measures. The primary outcome for the trial is the proportion of participants who maintain sustained abstinence for 24 weeks after their quit day. Abstinence is defined using the Russell 6 standard (i.e. fewer than 5 incidents of smoking from the quit date, including all participants lost to follow-up as failed treatment, and confirming all successful quits via breath carbon monoxide testing). The intention to treat principle will be followed, and those lost to follow-up will be considered as a failed quit (8).

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Secondary Outcome Measures. The following secondary outcome measures are being assessed in all participants at 4, 12 and 24 weeks post quit date: Self-reported maintenance of smoking cessation: measured by current cessation, number of cigarettes in past week/month/since last session; Use of Nicotine replacement therapy/nicotine containing products: Participants will be asked to answer Yes/No to the following: 'Since we last met, have you regularly used any of the following?' and 'Are you planning on using any of the following in the future?' E-cigarettes, Nicotine Patches, Nicotine Gum, Other; Perceived value of being nicotine free: measured on a scale of 1-7 (strongly disagree - strongly agree) to the following items: 'Being nicotine free is of value to me', 'I value being nicotine free', 'Having no nicotine in my system is / would be beneficial to me'; Satisfaction with Life (9): A well validated 5-item scale designed to measure global cognitive judgements of one's life satisfaction. Participants indicate how much they agree or disagree with each of the 5-items using a scale of 1-7 (strongly disagree - strongly agree); Quit efficacy: measured on a scale of 1-7 (strongly disagree - strongly agree) to the following items: 'I can achieve my aims to quit smoking', 'I can cope with the demands of quitting smoking', 'It is unlikely that I will do well at quitting smoking', 'I think I can perform well at quitting smoking'. Readiness to change smoking behaviour (10): A well-validated measure of readiness to consider smoking cessation. Measured on a scale of 1 (lowest level of readiness) to 10 (highest level of readiness). Responses 1-3 are indicative of no plans to quit smoking, 4-6 range from thinking about quitting to planning to quit in the next six months, and 7-10 range from planning to quit in the next 30 days to having already quit smoking. Adverse events: Information regarding any adverse events relating to the participant’s health and wellbeing and whether they are related to treatment.

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Sample size Based on data from Dijkstra et al. (7), an attrition rate between recruitment and final follow up (at 6 months) of 30% is indicated. To ensure sufficient participants in the final sample at this rate, an initial sample of 620 participants will be sought (310 per intervention group). To detect differences in success rates (at 6 months) in treatments with success rates of 30% and 50% respectively (powered at .95, alpha 0.05, and adjusting to account for a 25% loss to 6 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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follow up) a sample size of 480 would be required. To detect differences between 20% and 40% quit rates (with the same assumptions) a sample of 400 would be required. To detect differences between 50% and 70% a sample size of 566 is needed. Thus, the study will be adequately powered to detect meaningful differences in the expected range, with loss to follow up rates in the region of previous research or somewhat above. Recruitment People will be informed of the trial through local placement of posters, leaflets to residential properties, booklets to major employers, employment networks and councils, webpages at LSBU and social media campaigns. People interested in enrolling will be invited to contact London South Bank University to provide contact details. Within a few days, ppotential participants will be contacted by phone and undergo eligibility pre-screening. If eligible, participants will be asked about demographics, smoking dependence and prior quit attempts to allow for stratified randomisation into the trial. The researcher will gain signed consent via post or scanned email before inviting them to attend LSBU for completion of baseline measures. As this stage is before intention to treat or condition allocation, no restrictions on contact attempts are placed on this stage.

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Randomisation, allocation concealment and sequence generation Potential participants will be told about the trial and asked if they would like to take part by a research assistant. If interested, they will be asked for basic demographic data (e.g. age, sex, ethnicity) and checked to see if they meet the trial inclusion. Those who provide further details about their level of nicotine dependence (determined by the Fagerstrom Test for Nicotine Dependence [FTND] questionnaire (11)) will be randomised to condition by Sarah White (study statistician) using the Kang and Park (12) ‘Covariate Adaptive Randomization Program’ (Version 1.0) software package. Four stratification factors, each at two levels, will be used: nicotine dependence, number of prior quit attempts, age and gender. Participants will be assigned to the ACE and NHS 1-1 intervention groups in a ratio of 1.1 (310 in each).

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Email accounts ‘A’ and ‘B’ will be allocated randomly to each clinical team by the statistician. The randomisation allocator will randomise to condition A or B and will send an email message to account A or B with participant details. The clinical team will then contact participants to start treatment. Members of the trial steering committee, management committee, and other team members will remain blind to treatment allocation until the last follow-up is completed and the data recorded, and the clinical team is not authorised to reveal it. Should for medical or other reasons, a participant’s condition need to be unblinded, the randomisation allocator will communicate the participant’s intervention (not their A/B status) to the research team. The date this participant was unblinded will be noted on the Master Data File. 7 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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Withdrawal criteria Should participants require discontinuation of the study treatment for any reason, data collection will continue as scheduled as if they were continuing with the randomised treatment. If the participant ceases treatment due to a serious adverse event, they will be followed until the event resolves. Serious adverse events occurring within a month of discontinuation will be reported to the project lead. Data collection, management and analysis All data will be collected via paper questionnaires, apart from carbon monoxide readings where a Smokerlyzer piCO analyser will be used. Paper documentation will be stored only on LSBU premises, in a locked filing cabinet. The exception to this is that clinical teams can hold their own scheduling materials (these will be encrypted if electronic, or stored in a locked location). Consent forms will be stored in a separate location to all other hard copy data. All electronic documents will be held only on LSBU secure servers. A single identifiable and definitive copy of each document (including the data file) will be maintained. Should a manual transfer of data via USB or CD be required, such media will be encrypted. Any laptops used will be encrypted with Sophos Safeguard. Data will be held on university servers, which are on the IBM cloud system (and protected by their firewalls etc.).

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The participant master sheet with identifiable information to participant numbers will be locked with a password known only to the research team. Participant data will only be linked directly with their participant ID code. Personal data (e.g. identifiable data) will be accessible to the research team (as part of the screening process), the statistician and the direct care team. All LSBU employees are required to undergo mandatory data protection training. Hard copies of data will be destroyed via confidential waste disposal five years after the research findings have been published. Electronic copies of data will be stored in two archives. In both cases, only anonymous data will be archived. They will be archived at London South Bank Data Archive and a national data repository such as the UK Data Archive.

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Data verification

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The accuracy of data recorded will be periodically verified against source documentation at each wave point. At each point, the data for that wave will be verified against 10% of participants (5% per condition). These will be sampled randomly and verified by an auditor independent to the project team and statistical team. The results of this verification (in % accuracy) will be reported to the project management team, the statistical team and the project advisory board. Statistical analyses A senior statistician determined the sample size and wrote the statistical analysis plan which was subsequently agreed by the Steering committee. All statistical analyses will be 8 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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performed using SPSS version 24 software. Participants will be analysed on an intention to treat basis at the point of randomisation. 95% confidence intervals will be presented for all analyses. Missing data will be replaced by the mean within condition score. These covariates have been selected as they have been shown to influence treatment success, and we wish to investigate the unique effects of treatment across a demographically heterogeneous sample. Primary outcome analysis. Participants for whom smoking cessation cannot be confirmed (i.e. are lost to follow-up) will be included in the analysis as failed quits, in line with the Russell 6 Standard. Logistic regression will be used to estimate the effectiveness of the treatment condition upon smoking cessation at six months. The stratification variables will be included as covariates.

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Secondary smoking outcomes. To investigate if the differential effects of interventions are present at each time point (4 and 12 weeks), the primary analysis will be repeated twice, replacing the outcome measure with smoking cessation confirmed at 4 and 12 weeks respectively. To evaluate the differences between treatment arms only amongst participants who did not ‘reset’ their quit dates (NHS arm) or attended a top-up session (ACE arm), the primary analysis will be repeated on smoking cessation outcomes at both 12 and 24 weeks. However, in these analyses, all participants who used a top-up session or a quit reset will be excluded. This is preferable to including them as failed quits, as many may in fact be successful cessations, whilst also attending a top-up. Use of NRT in each treatment arm will be tested by conducting a logistic regression with the covariates outlined above. Treatment arm and treatment success will be included as the independent variables.

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Secondary non-smoking outcomes analyses. To analyse the take up of treatment between conditions, a logistic regression will be undertaken on treatment completion (operationalised as attendance at the ACE session and attendance at all five weeks of the NHS sessions), including the same covariates specified in the main analysis. Multi-level regression models with the same covariates as the main analysis and time of measurement (4 weeks, 12 weeks and 24 weeks) will be undertaken with perceived value of being nicotine free, readiness to change, intentions to reengage, life satisfaction as the dependent variables. Planned comparisons between treatment arms at each time point will be undertaken.

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Plan of presentation. The disposition of participants who contacted the research team, were deemed eligible/ineligible, were randomised to each arm, received treatment and received follow-up at each time point will be presented in a CONSORT diagram. The number of eligible and ineligible participants, reasons for ineligibility, number of withdrawals and number of lost to follow ups per treatment arm will be reported. A table detailing any protocol violations and subsequent actions will be presented. The results of the data validation exercises, as well as any resulting remedial action will be prepared. Treatment validation exercises and any resulting remedial action, the number and type of adverse 9 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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events identified, alongside any recorded outcomes will be reported. The number and type of protocol deviations identified, alongside any remedial outcomes will be discussed. The baseline characteristics (age, gender, nicotine dependence, prior quit attempts) will be broken down by treatment arm. Dissemination At the end of the study, a non-technical summary of the results will be prepared for participants. Two articles will be submitted to international peer-reviewed journals; 1) results from the general smoking population and 2) results from analysis of secondary outcome analysis. The results from these articles will be presented at national and international academic/healthcare conferences. Funding

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This trial is funded in full by Allen Carr’s Easyway (International) Ltd. The NHS smoking cessation intervention is provided by Lambeth Stop Smoking Service. The design, conduct, data collection, analyses and interpretation of the trial are conducted by LSBU, independent from Allen Carr’s Easyway (International) Ltd. Based on the findings, papers for publication will be prepared by the research team at LSBU who will have ultimate authority over these activities.

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Contributors

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DF, IA and TM conceived the design of the trial and secured funding. DF wrote the study protocol. KVW manages the day to day running of the trial. SW will undertake all data analyses. This protocol paper was written by KVW with input from all co-authors. DF is guarantor for this paper. All authors read and approved the final manuscript.

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This protocol has been independently peer reviewed by Professor Robert West, University College London and meets requirements of London - Fulham Research Ethics Committee, reference number 16/LO/1657. Competing interest: None declared.

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Roles and responsibilities Monitoring of the progress of the trial will be conducted by three committees/groups. The three committees will consist of an Advisory Committee, a Steering Committee and a Data Monitoring Committee (see Table 1. for composition of committee members).


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Table 1. Composition of committee members Chief Investigator

Dr. Daniel Frings (Principle Investigator), Associate Professor of Psychology, Division of Psychology, School of Applied Sciences, London South Bank University, 02078157815, [email protected]

Trial Coordinator

Dr Kerry Wood, Clinical trial manager/research Fellow, Division of Psychology, School of Applied Sciences, London South Bank University, 02078157185 [email protected] London South Bank University John Dicey, Worldwide Managing Director & CEO, Allen Carr's Easyway (International) Ltd, Park House, 14 Pepys Road, Raynes Park, London SW20 8NH, England [email protected] John Dicey, Worldwide Managing Director & CEO, Allen Carr's Easyway (International) Ltd, Park House, 14 Pepys Road, Raynes Park, London SW20 8NH, England [email protected]

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Sponsor Joint-sponsor(s)/cosponsor(s)

Funder(s)

NHS stop smoking service

Gareth Absalom, Team Leader, Lambeth Stop Smoking Service, [email protected] Dr. Tony Moss, Director of Education and Student Experience, Division of Psychology, School of Applied Sciences, London South Bank University, [email protected] Prof. Ian Albery, Professor of Psychology and Director of Research and Enterprise, School of Applied Sciences, London South Bank University, [email protected] Dr Kerry Wood, Clinical trial manager/research Fellow, Division of Psychology, School of Applied Sciences, London South Bank University, 02078157185 [email protected] Dr Sarah White, Population Health Research Institute St George’s University of London, Cranmer Terrace London, SW17 0RE, 02087253615, [email protected] Professor Robert West: Professor of Health Psychology and Director of Tobacco Studies, Cancer Research UK Health Behaviour Unit, Department of Epidemiology and Public Health, University College London, [email protected]. Ms. Jacqui Leslie, Service Improvement Lead, Medway NHS Foundation Trust, [email protected]. Dr. Lynne Dawkins, Associate Professor in Psychology, London South Bank University, School of Applied Sciences, [email protected].

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Project management team

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Dr Rachel Taylor, Senior Research Manager, Cancer Clinical Trials Unit, University College London Hospitals NHS Foundation Trust, 1st Floor East, 250 Euston Road, London NW1 2PG, (0) 7967 012909, [email protected] Advisory Committee consists of the project management team and research fellow, 2 independent academic experts in smoking cessation, a public health practitioner in a relevant field, and a service user. This groups purpose will be to review the trials formation and progress, and give its views on the standards of the study, and comment on any requirements for protocol amendments if need arises. Steering Committee consists of the project management team and the research fellow. This group will consider the views of the Advisory Group and will make decisions on the operation of the trial, including any decisions regarding protocol changes. Data Monitoring Committee consists of the project director, research fellow, internal statistical lead and an independent statistical advisor. It will oversee the quality control of the data arising from the study and the planning and implementation of the analytical strategy. It will be the only committee with access to unblinded data.

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REFERENCES 1. World Health Organisation. Global report on trends in prevalence of tobacco smoking.2015.http://www.who.int/tobacco/publications/surveillance/reportontren dstobaccosmoking/en/. 2. Health and Social Care Information Centre. Statistics on smoking. 2016. http://content.digital.nhs.uk/catalogue/PUB20781/stat-smok-eng-2016-rep.pdf 3. Bucchalter, A.R., Acosta, M.C., Evans, S.E., Breland, A.B., & Eissenberg, T. (2015). Tobacco abstinence symptom suppression: the role played by the smoking-related stimuli that are delivered by denicotinized cigarettes. Addiction, 100, 550-559. 4. Ronckers, E.T., Groot, W., & Ament, A.J. (2005). Systematic review of economic evaluations of smoking cessation: standardizing the cost-effectiveness. Medical Decision Making, 25, 437-448. 5. Stead, L.F., Perera, R., Bullen, C., Mant, D., Hartmann-Boyce, J., Cahill, K., & Lancaster, T. (2012). Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews, 11. Art. No.: CD000146. Doi:10.1002/14651858.CD000146.pub4. 6. Public Health England (2016). Health matters: Smoking and quitting in England. https://www.gov.uk/government/publications/health-matters-smoking-andquitting-in-england/smoking-and-quitting-in-england 7. Dijkstra, A., Zuidema, R., Vos., D., & van Kalken, M. (2014). The effectiveness of the Allen Carr smoking cessation training in companies tested in quasi experimental design. BMC Public Health, 14, 952. 8. West, J., Hajek, P., Stead, L., & Stapleton, J. (2005). Outcome criteria in smoking cessation trials: proposal for a common standard. Addiction, 100, 299-303. 9. Diener, E., Emmons, R.A., Larsen, R.J., & Griffin, S. (1985). The satisfaction with life scale. Journal of Personality Assessment, 49, 71-75. 10. Beiner, L., & Abrams, D.B. (1991). The Contemplation Ladder: validation of a measure of readiness to consider smoking cessation. Health Psychology, 10, 360-365. 11. Heatherton, F., Kozlowski, L.T., Frecker, R.C., & Fagerstrom, K.O. (1991). The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. British Journal of Addiction, 86, 1119-27. 12. Kang, M., Ragan, B.G., & Park, J-H. (2007). Issues in Outcomes Research: An Overview of Randomization Techniques for Clinical Trials. Journal of Athletic Training, 43, 215-221.

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CONSORT 2010 checklist of information to include when reporting a randomised trial* Section/Topic

Item No Checklist item

Title and abstract

Reported on page No

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Identification as a randomised trial in the title Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts)

1 2

2a 2b

Scientific background and explanation of rationale Specific objectives or hypotheses

3 3

Outcomes

6a

Sample size

6b 7a 7b

Description of trial design (such as parallel, factorial) including allocation ratio Important changes to methods after trial commencement (such as eligibility criteria), with reasons Eligibility criteria for participants Settings and locations where the data were collected The interventions for each group with sufficient details to allow replication, including how and when they were actually administered Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed Any changes to trial outcomes after the trial commenced, with reasons How sample size was determined When applicable, explanation of any interim analyses and stopping guidelines

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Interventions

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Introduction Background and objectives Methods Trial design Participants

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Randomisation: Sequence generation Allocation concealment mechanism Implementation

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Method used to generate the random allocation sequence Type of randomisation; details of any restriction (such as blocking and block size) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned

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10

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Blinding

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Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions If done, who was blinded after assignment to interventions (for example, participants, care providers, those

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Statistical methods Results Participant flow (a diagram is strongly recommended) Recruitment

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assessing outcomes) and how If relevant, description of the similarity of interventions Statistical methods used to compare groups for primary and secondary outcomes Methods for additional analyses, such as subgroup analyses and adjusted analyses

Ancillary analyses

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Harms

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Discussion Limitations Generalisability Interpretation

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Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses Generalisability (external validity, applicability) of the trial findings Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence

Other information Registration Protocol Funding

23 24 25

Registration number and name of trial registry Where the full trial protocol can be accessed, if available Sources of funding and other support (such as supply of drugs), role of funders

Outcomes and estimation

13b 14a 14b 15 16 17a

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For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome For each group, losses and exclusions after randomisation, together with reasons Dates defining the periods of recruitment and follow-up Why the trial ended or was stopped A table showing baseline demographic and clinical characteristics for each group For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) For binary outcomes, presentation of both absolute and relative effect sizes is recommended Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory All important harms or unintended effects in each group (for specific guidance see CONSORT for harms)

Baseline data Numbers analysed

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*We strongly recommend reading this statement in conjunction with the CONSORT 2010 Explanation and Elaboration for important clarifications on all the items. If relevant, we also recommend reading CONSORT extensions for cluster randomised trials, non-inferiority and equivalence trials, non-pharmacological treatments, herbal interventions, and pragmatic trials. Additional extensions are forthcoming: for those and for up to date references relevant to this checklist, see www.consort-statement.org.


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BMJ Open bmjopen-2017-016867.R1 Protocol 03-Jul-2017


Keywords:

Public health

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Wood, Kerry; London South Bank University, Psychology Albery, Ian; London South Bank University, Department of Psychology Moss, Anthony ; London South Bank University, Psychology White, Sarah; St George's University of London, Division of Population Health Sciences and Education Frings, Daniel; London South Bank University, Division of Psychology


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Kerry V. Wood1, Ian P. Albery1, Antony C. Moss1, Sarah White2, Daniel Frings1

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ABSTRACT Introduction: Smoking is a major cause of ill health and is associated with several diseases including cancer, coronary heart disease and stroke. Many psychological and pharmacological smoking cessation treatments are available and although they are undoubtedly the most cost-effective health interventions available, many people still fail to maintain cessation in the long-term. Recently NICE called for comparative studies to determine the short- and long-term effectiveness of Allen Carr's Easyway (ACE) method of stopping smoking. This study will compare the efficacy of the ACE programme and a 1-1 counselling service available via the NHS. Methods and analysis: A two-arm, parallel-group, blinded, randomised controlled trial will be conducted with people who smoke tobacco cigarettes, aged 18 or over and are motivated to quit. Exclusion criteria comprise mental health condition, pregnancy or respiratory disease such as chronic obstructive pulmonary disease or emphysema. The primary treatment outcome is smoking cessation 26 weeks after treatment. Participants will be analysed on an intention to treat basis at the point of randomisation. Before being randomised the research team will not inform participants which two treatments are being compared. Once randomised researchers will be blind to participant condition, and participants blind to the condition they are not assigned to. Logistic regression will be used to estimate the effectiveness of the treatment condition upon smoking cessation at six months. The following covariates will be included: baseline quit efficacy (at inclusion), age (at inclusion), gender and baseline nicotine dependency. Ethics and Dissemination: Approval was granted by London – Fulham Research Ethics Committee (ref: 16/LO/1657). The study’s findings will be published in peer-reviewed journals and disseminated at national and international conferences. Trial Registration: ClinicalTrials.gov Identifier Number NCT02855255; ISRCTN registration number: ISRCTN23584477.

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STRENGTHS AND LIMITATIONS Strengths • This study adopted a Blinded Randomised Controlled Trial design • Chemical verification of quit success • Comparison of two common smoking cessation interventions Limitations • No ‘no treatment’ control • Although researchers are blinded, therapists delivering the interventions are not blinded i.e. each intervention is delivered by experienced facilitators for NHS and ACE separately.

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INTRODUCTION Dependence on nicotine has long been a problem and although statistics from the World Health Organization (1) show that the prevalence of tobacco smoking is declining worldwide, there are still a significant number of people, 1.1 billion in 2015, who continue to smoke (1) Smoking is a major cause of ill health and is associated with several diseases including cancer, coronary heart disease, and stroke. In the UK alone in 2014, there were 9.6 million smokers, with 78,000 deaths attributed to smoking (2). Many smokers want to quit and often make several attempts to do so, but the majority fail due to both physiological and psychological factors (3). Over the years, researchers have sought to develop effective cessation treatments in an effort to provide education and support. Consequently, many psychological and pharmacological treatments are available to help smokers quit, and although these types of intervention are undoubtedly the most costeffective interventions available (4), many people fail to maintain smoking cessation in the longer term (5). In 2014, it was reported that 37% of smokers made an attempt to quit but only 19% were actually successful (6).

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It is important to understand the relative efficacies of various interventions designed to help people quit, and recently NICE called for comparative studies to determine the short- and long-term effectiveness of Allen Carr's Easyway (ACE) method of stopping smoking. Whilst the ACE programme is well-established and its efficacy has received some empirical support (see Dijkstra et al. [7]), there has not to date been a randomised control trial testing the efficacy of this programme. Consequently, Allen Carr's Easyway to stop smoking and a 1-1 counselling service available via the NHS will be compared. By comparing the ACE program to a NHS delivered treatment program, an estimate of the relative effectiveness of ACE in comparison to the NHS service can be made. This will potentially inform future judgements about the use of this method by private and public health care providers. The findings will add to the evidence base around the use of the NHS stop smoking service and the Allen Carr’s Easyway method.

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METHODS/DESIGN Design

A two-arm, parallel-group, blinded1, randomised controlled trial.

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Treatment setting/site All intervention sessions for the NHS and ACE programmes will be delivered on the London South Bank University (LSBU) Southwark campus and the Allen Carr’s Easyway site in London, SW20. They begin in February 2017 and will run for eight months. 1

With researchers blind to participant condition, and participants blind to the condition they are not assigned to


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Study population People who smoke tobacco cigarettes and are motivated to quit. Inclusion and exclusion criteria Participants will be eligible provided they are at least 18 years of age, are current smokers who intend to quit and are prepared to be assigned randomly to one of two treatment conditions. Individuals who, on being asked at the point of recruitment would prefer an NHS provided treatment, are currently in another RCT or similar research project, disclose that they have a mental health condition, are pregnant or have a respiratory disease such as chronic obstructive pulmonary disease or emphysema will be excluded. Additionally, individuals who feel they are unable to reach the treatment location (London South Bank University’s Southwark Campus or London SW20) for treatment and follow-up will also be excluded.

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Interventions

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Allen Carr’s Easyway programme. The ACE intervention involves a single group session with up to 25 attendees, led by a trained facilitator. The five to six-hour session broadly comprises elements of CBT and ends with a short hypnotherapy/relaxation exercise. Participants are encouraged to carry on smoking as normal right up until they attend the clinic and during the session are encouraged to smoke as normal during scheduled smoking breaks (around every 45-60 minutes). Participants are assisted in identifying positive expectancies they associate with smoking (e.g. pleasure, support, crutch, or other benefits) before working towards the conclusion that the belief that smoking provides these benefits is, in fact, erroneous and harmful. Participants also achieve a basic understanding of how the psychological and pharmacological mechanisms of nicotine addiction facilitate the maintenance of erroneous and problematic beliefs. These sessions end with a ‘ritual’ final cigarette followed by an approximately 20-minute period of hypnotherapy – a light relaxation exercise that reinforces the main points of the session. At the end of each session each participant is asked to make a written record of what it was about their life as a smoker that made them want to stop. Following each session, the clinical team will call, email, or SMS text the participant on day 1, and again at 3, 7, 10, 14, 21, 30, 45, 60, 75, and 90 days with a short courtesy message such as “Hope you’re well. Please don’t hesitate to get in touch if you have any questions at all”, “Hope all is well with you. Don’t forget we’re here if you have any questions”.

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NHS smoking cessation programme. The NHS intervention comprises the NHS stop smoking service currently offered at Guy’s and St Thomas’ NHS Foundation Trust and Lambeth Public Health. This constitutes a single session of around 30 minutes which combines motivational interviewing and CBT, followed by four follow-up sessions. The initial session involves informing the client about the treatment programme, assessing current smoking, readiness to quit and past quit attempts. Participants are then advised on the operation of nicotine 4 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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dependence, the mechanics of withdrawal, and given advice on changing routine. The use, pros and cons of various Nicotine Replacement Therapies (NRTs) are also outlined. A quit date is set (within two weeks of receiving the intervention) and the importance of complete abstinence discussed. Finally, a carbon monoxide test is administered, and explained. Before the session finishes, participants are assisted in identifying high risk situations in the coming week, and develop quit action plans. This treatment is combined with prescribed NRT of the patients’ choice (including Varenicline). One, two and three weeks’ post quit date, shorter meetings (approximately 10 minutes) are arranged. These involve a progress check, a discussion around withdrawal symptoms and coping, a check on NRT supplies, a reflection on difficult situations encountered, a carbon monoxide test and planning for high risk situations in the coming week. The importance of abstinence is finally reinforced. Four weeks after the quit date, an approximately 10minute meeting checks on progress, measures carbon monoxide, advises on continued use of medication, discusses craving and urges and difficult situations and finally reinforces the importance of complete abstinence.

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Top-ups and Resets. Both treatments contain as standard, options to reset/top up quit dates. The ACE provision includes the option for clients to ‘top-up’ their treatment in two further sessions. These second and third sessions broadly follow the same format (approximately 3.5 hours) but contain more interaction and a smaller group (up to 15 clients) and either be carried out face-to-face or online. They can take place up to three months from the initial session. The clinician will provide contact details through which these sessions can be arranged. Should these optional sessions be taken up by a participant then the use of a top-up, and the date will be recorded by the clinician on the participant schedule and the subsequent testing dates will be based on the reset date. The primary outcome will be counted from the reset date (e.g. prior cigarettes consumed up to that point will be disregarded). The NHS arm contains the option for participants to be given a chance to reset their quit date, at the discretion and suggestion of the clinician. Should a reset be offered, the use of a reset and the revised date will be recorded, and the subsequent testing dates will be based on the reset date. The primary outcome will be counted from the reset date (i.e. prior cigarettes consumed up to that point will be disregarded).

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Insert Figure 1. Process diagram

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Outcomes Primary Outcome Measures. The primary outcome for the trial is the proportion of participants who maintain sustained abstinence for 26 weeks after their quit date. Abstinence is defined using the Russell 6 standard (i.e. fewer than 5 incidents of smoking from the quit date, including all participants lost to follow-up as failed treatment, and confirming all successful quits via breath carbon monoxide testing). The intention to treat principle will be followed, and those lost to follow-up will be considered as a failed quit (8).


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Secondary Outcome Measures. The following secondary outcome measures are being assessed in all participants at 4, 12 and 26 weeks post quit date: Self-reported maintenance of smoking cessation: measured by current cessation, number of cigarettes in past week/month/since last session; Use of Nicotine replacement therapy/nicotine containing products: Participants will be asked to answer Yes/No to the following: 'Since we last met, have you regularly used any of the following?' and 'Are you planning on using any of the following in the future?' E-cigarettes, Nicotine Patches, Nicotine Gum, Other; Perceived value of being nicotine free: measured on a scale of 1-7 (strongly disagree - strongly agree) to the following items: 'Being nicotine free is of value to me', 'I value being nicotine free', 'Having no nicotine in my system is / would be beneficial to me'; Satisfaction with Life (9): A well-validated 5-item scale designed to measure global cognitive judgements of one's life satisfaction. Participants indicate how much they agree or disagree with each of the 5-items using a scale of 1-7 (strongly disagree - strongly agree); Quit efficacy: measured on a scale of 1-7 (strongly disagree - strongly agree) to the following items: 'I can achieve my aims to quit smoking', 'I can cope with the demands of quitting smoking', 'It is unlikely that I will do well at quitting smoking', 'I think I can perform well at quitting smoking'. Readiness to change smoking behaviour (10): A well-validated measure of readiness to consider smoking cessation. Measured on a scale of 1 (lowest level of readiness) to 10 (highest level of readiness). Responses 1-3 are indicative of no plans to quit smoking, 4-6 range from thinking about quitting to planning to quit in the next six months, and 7-10 range from planning to quit in the next 30 days to having already quit smoking. Adverse events: Information regarding any adverse events relating to the participant’s health and wellbeing and whether they are related to treatment.

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Based on data from Dijkstra et al. (7), an attrition rate between recruitment and final follow up (at 6 months) of 30% is indicated. To ensure sufficient participants in the final sample at this rate, an initial sample of 620 participants will be sought (310 per intervention group). To detect differences in success rates (at 6 months) in treatments with success rates of 30% and 50% respectively (powered at .95, alpha 0.05, and adjusting to account for a 25% loss to follow up) a sample size of 480 would be required. To detect differences between 20% and 40% quit rates (with the same assumptions) a sample of 400 would be required. To detect differences between 50% and 70% a sample size of 566 is needed. Thus, the study will be adequately powered to detect meaningful differences in the expected range, with loss to follow up rates in the region of previous research or somewhat above.

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Recruitment People will be informed of the trial through local placement of posters, leaflets to residential properties, booklets to major employers, employment networks and councils, 6 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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webpages at LSBU and social media campaigns. People interested in enrolling will be invited to contact London South Bank University to provide contact details and will be sent (via email or post) an information sheet containing written information about the study. Within two days, potential participants will be contacted by phone and undergo eligibility prescreening. At this point they will not be informed which two interventions are being compared in the study. If eligible, participants will be asked about demographics, nicotine dependence and prior quit attempts to allow for stratified randomisation into the trial. Within two days of being screened the research team will send eligible participants a consent form (via post or email). As this stage is before intention to treat or condition allocation, no restrictions on contact attempts are placed on this stage. On gaining written consent, participant’s details will be sent to the independent randomiser for allocation. Once randomised, participants will see the research team four times (baseline, 4 weeks, 12 weeks and 26 weeks). They will be paid £15 cash for attending each measurement point and regardless of quit outcome, they will be entered into a prize draw to win a Caribbean holiday for two, an iPad or gym membership.

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Randomisation, allocation concealment and sequence generation Participants will be randomised to condition by Sarah White (study statistician) using the Kang and Park (11) ‘Covariate Adaptive Randomization Program’ (Version 1.0) software package. Four stratification factors, each at two levels, will be used: nicotine dependence (determined by the Fagerstrom Test for Nicotine Dependence [FTND] questionnaire (12)), number of prior quit attempts, age and gender. Participants will be assigned to the ACE and NHS 1-1 intervention groups in a ratio of 1.1 (310 in each). Blinding

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Participants will be blind to both interventions until randomised and once allocated will be blind to the alternative intervention. Members of the trial steering committee, management committee, and other team members (with the exception of the statistician/randomiser), will remain blind to treatment allocation until the last follow-up is completed and the data recorded, and the clinical team is not authorised to reveal it. Data collection, management and analysis

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All data will be collected via paper questionnaires, apart from carbon monoxide readings where a Smokerlyzer piCO analyser will be used. Participant data will only be linked directly with their participant ID code. Personal data (e.g. identifiable data) will be accessible to the research team (as part of the screening process), the statistician and the direct care team. Hard copies of data will be destroyed via confidential waste disposal five years after the research findings have been published. Electronic copies of data will be stored in two archives. In both cases, only anonymous data will be archived. They will be archived at London South Bank Data Archive and a national data repository such as the UK Data Archive.


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Statistical analyses A senior statistician determined the sample size and wrote the statistical analysis plan which was subsequently agreed by the Steering committee. All statistical analyses will be performed using SPSS version 24 software. Participants will be analysed on an intention to treat basis at the point of randomisation. 95% confidence intervals will be presented for all analyses. Missing data will be replaced by the mean within condition score. The following stratification variables will be included as covariates in all regression models: baseline quit efficacy (at inclusion), age (at inclusion), gender and baseline nicotine dependency. These covariates have

been selected as they have been shown to influence treatment success, and we wish to investigate the unique effects of treatment across a demographically heterogeneous sample.

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Primary outcome analysis. Participants for whom smoking cessation cannot be confirmed (i.e. are lost to follow-up) will be included in the analysis as failed quits, in line with the Russell 6 Standard. Logistic regression will be used to estimate the effectiveness of the treatment condition upon smoking cessation at six months.

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A series of sensitivity analyses will be conducted to assess the robustness of primary results with regards to definition of the primary outcome. To investigate if the differential effects of interventions are present at each time point (4 and 12 weeks), the primary analysis will be repeated twice, the dependent variable being smoking cessation confirmed at 4 and 12 weeks. The primary analysis will be repeated on smoking cessation outcomes at both 12 and 26 weeks using only participants who did not ‘reset’ their quit dates (NHS arm) or attended a top-up session (ACE arm). This is preferable to including them as failed quits, as many may in fact be successful cessations, whilst also attending a top-up.

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Secondary smoking outcomes. Use of NRT in each treatment arm will be tested by conducting a logistic regression. Treatment arm and treatment success will be included as the independent variables. Secondary non-smoking outcomes analyses. To analyse the take up of treatment between conditions, a logistic regression will be undertaken on treatment completion (operationalised as attendance at the ACE session and attendance at all five weeks of the NHS sessions). Multi-level regression models with time of measurement (4 weeks, 12 weeks and 26 weeks) will be undertaken with perceived value of being nicotine free, readiness to change, intentions to reengage, life satisfaction as the dependent variables, treatment arm as independent variable. Planned comparisons between treatment arms at each time point will be undertaken.

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Plan of presentation. A CONSORT diagram will be used to describe the sampling, drop-outs and randomisation. Funding This trial is funded in full by Allen Carr’s Easyway (International) Ltd. The NHS smoking cessation intervention is provided by Lambeth Stop Smoking Service. The design, conduct, 8 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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data collection, analyses and interpretation of the trial are conducted by LSBU, independent from Allen Carr’s Easyway (International) Ltd. Based on the findings, papers for publication will be prepared by the research team at LSBU who will have ultimate authority over these activities. The research team are contractually free to publish whatever findings the study produces, ACE has no veto over publication, but will be given advanced notice of the findings prior to publication. Contributors 2 Ethics

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This protocol has been independently peer reviewed by Professor Robert West, University College London and meets requirements of London - Fulham Research Ethics Committee, reference number 16/LO/1657. Competing interest: No Authors have any conflicts of interest with NHS stop smoking services, or Allen Carr’s Easyway to declare. The authors have no financial relationship or interest with the funding organisation.

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Acknowledgements: We would like to acknowledge Lambeth Public health for their support with this study.

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DF, IA and AM conceived the design of the trial and secured funding. DF wrote the study protocol. KVW manages the day to day running of the trial. SW will undertake all data analyses. This protocol paper was written by KVW with input from all co-authors. DF is guarantor for this paper. All authors read and approved the final manuscript.


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REFERENCES 1. World Health Organisation. Global report on trends in prevalence of tobacco smoking.2015.http://www.who.int/tobacco/publications/surveillance/reportontren dstobaccosmoking/en/. 2. Health and Social Care Information Centre. Statistics on smoking. 2016. http://content.digital.nhs.uk/catalogue/PUB20781/stat-smok-eng-2016-rep.pdf 3. Bucchalter, A.R., Acosta, M.C., Evans, S.E., Breland, A.B., & Eissenberg, T. (2015). Tobacco abstinence symptom suppression: the role played by the smoking-related stimuli that are delivered by denicotinized cigarettes. Addiction, 100, 550-559. 4. Ronckers, E.T., Groot, W., & Ament, A.J. (2005). Systematic review of economic evaluations of smoking cessation: standardizing the cost-effectiveness. Medical Decision Making, 25, 437-448. 5. Stead, L.F., Perera, R., Bullen, C., Mant, D., Hartmann-Boyce, J., Cahill, K., & Lancaster, T. (2012). Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews, 11. Art. No.: CD000146. Doi:10.1002/14651858.CD000146.pub4. 6. Public Health England (2016). Health matters: Smoking and quitting in England. https://www.gov.uk/government/publications/health-matters-smoking-andquitting-in-england/smoking-and-quitting-in-england 7. Dijkstra, A., Zuidema, R., Vos., D., & van Kalken, M. (2014). The effectiveness of the Allen Carr smoking cessation training in companies tested in quasi experimental design. BMC Public Health, 14, 952. 8. West, J., Hajek, P., Stead, L., & Stapleton, J. (2005). Outcome criteria in smoking cessation trials: proposal for a common standard. Addiction, 100, 299-303. 9. Diener, E., Emmons, R.A., Larsen, R.J., & Griffin, S. (1985). The satisfaction with life scale. Journal of Personality Assessment, 49, 71-75. 10. Beiner, L., & Abrams, D.B. (1991). The Contemplation Ladder: validation of a measure of readiness to consider smoking cessation. Health Psychology, 10, 360-365. 11. Kang, M., Ragan, B.G., & Park, J-H. (2007). Issues in Outcomes Research: An Overview of Randomization Techniques for Clinical Trials. Journal of Athletic Training, 43, 215-221. 12. Heatherton, F., Kozlowski, L.T., Frecker, R.C., & Fagerstrom, K.O. (1991). The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. British Journal of Addiction, 86, 1119-27.

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Process diagram

Potential participant contacts the Research team by phone or email.

Research team allocates participant number

Research team screens by phone or email using screening packet No exclusion criteria but not in preparation phase. Two week delay and re-contact. Three attempts before screened out. With a ‘ did not complete eligibility screening’ outcome on screened out spreadsheet.

Screen out to NHS service via NHS clinical team. Note on screened out spreadsheet.

Meets exclusion criteria

Eligibility Eligible

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Research team: secures participant consent and hands participant details (and stratification details) to randomisation allocator via screening packet. Notes date consent received and date screened in on participant schedule

Randomisation allocator: Randomises to condition using covariate adaptive randomisation method to condition A or B.

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IINTENTION TO TREAT FROM AT THIS POINT

Notes date of randomisation on participant schedule Notes condition on participant condition sheet Notes an additional allocation on condition count sheet Sends message to account A or B with participant details

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Clinical team: Schedules treatment with participants from another email account. Three attempts to schedule treatment before participant recorded as LTF and entered onto screened out spreadsheet

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Prior to treatment makes an appointment for baseline on Baseline appointment sheet up to a week before treatment for WAVE 1. Notes date of quit date on participant schedule. For ACE this is the treatment date, for NHS, it is the agreed quit date, but within 2 weeks of the intervention.

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Resets / Top-up?

Research team: Schedules follow up waves 2, 3 and 4 using data from the participant schedule

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Reset is recorded on participant schedule, dates reset from that point

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CONSORT 2010 checklist of information to include when reporting a randomised trial* Section/Topic

Item No Checklist item

Title and abstract

Reported on page No

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Identification as a randomised trial in the title Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts)

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2a 2b

Scientific background and explanation of rationale Specific objectives or hypotheses

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Outcomes

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Sample size

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Description of trial design (such as parallel, factorial) including allocation ratio Important changes to methods after trial commencement (such as eligibility criteria), with reasons Eligibility criteria for participants Settings and locations where the data were collected The interventions for each group with sufficient details to allow replication, including how and when they were actually administered Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed Any changes to trial outcomes after the trial commenced, with reasons How sample size was determined When applicable, explanation of any interim analyses and stopping guidelines

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Interventions

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Introduction Background and objectives Methods Trial design Participants

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Randomisation: Sequence generation Allocation concealment mechanism Implementation

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Method used to generate the random allocation sequence Type of randomisation; details of any restriction (such as blocking and block size) Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned

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Blinding

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Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions If done, who was blinded after assignment to interventions (for example, participants, care providers, those


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Statistical methods Results Participant flow (a diagram is strongly recommended) Recruitment

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Ancillary analyses

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Harms

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Discussion Limitations Generalisability Interpretation

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Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses Generalisability (external validity, applicability) of the trial findings Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence

Other information Registration Protocol Funding

23 24 25

Registration number and name of trial registry Where the full trial protocol can be accessed, if available Sources of funding and other support (such as supply of drugs), role of funders

Outcomes and estimation

13b 14a 14b 15 16 17a

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For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome For each group, losses and exclusions after randomisation, together with reasons Dates defining the periods of recruitment and follow-up Why the trial ended or was stopped A table showing baseline demographic and clinical characteristics for each group For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) For binary outcomes, presentation of both absolute and relative effect sizes is recommended Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory All important harms or unintended effects in each group (for specific guidance see CONSORT for harms)

Baseline data Numbers analysed

13a

assessing outcomes) and how If relevant, description of the similarity of interventions Statistical methods used to compare groups for primary and secondary outcomes Methods for additional analyses, such as subgroup analyses and adjusted analyses

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*We strongly recommend reading this statement in conjunction with the CONSORT 2010 Explanation and Elaboration for important clarifications on all the items. If relevant, we also recommend reading CONSORT extensions for cluster randomised trials, non-inferiority and equivalence trials, non-pharmacological treatments, herbal interventions, and pragmatic trials. Additional extensions are forthcoming: for those and for up to date references relevant to this checklist, see www.consort-statement.org.


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BMJ Open bmjopen-2017-016867.R2 Protocol 20-Sep-2017


Keywords:

Public health

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Wood, Kerry; London South Bank University, Psychology Albery, Ian; London South Bank University, Department of Psychology Moss, Anthony ; London South Bank University, Psychology White, Sarah; St George's University of London, Division of Population Health Sciences and Education Frings, Daniel; London South Bank University, Division of Psychology


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Kerry V. Wood1, Ian P. Albery1, Antony C. Moss1, Sarah White2, Daniel Frings1

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ABSTRACT Introduction: Smoking is a major cause of ill health and is associated with several diseases including cancer, coronary heart disease and stroke. Many psychological and pharmacological smoking cessation treatments are available and although they are undoubtedly the most cost-effective health interventions available, many people still fail to maintain cessation in the long-term. Recently NICE called for comparative studies to determine the short- and long-term effectiveness of Allen Carr's Easyway (ACE) method of stopping smoking. This study will compare the efficacy of the ACE programme and a 1-1 counselling service available via the NHS. Methods and analysis: A two-arm, parallel-group, blinded, randomised controlled trial will be conducted with people who smoke tobacco cigarettes, aged 18 or over and are motivated to quit. Exclusion criteria comprise mental health condition, pregnancy or respiratory disease such as chronic obstructive pulmonary disease or emphysema. The primary treatment outcome is smoking cessation 26 weeks after treatment. Participants will be analysed on an intention to treat basis at the point of randomisation. Before being randomised the research team will not inform participants which two treatments are being compared. Once randomised researchers will be blind to participant condition, and participants blind to the condition they are not assigned to. Logistic regression will be used to estimate the effectiveness of the treatment condition upon smoking cessation at six months. The following covariates will be included: baseline quit efficacy (at inclusion), age (at inclusion), gender and baseline nicotine dependency. Ethics and Dissemination: Approval was granted by London – Fulham Research Ethics Committee (ref: 16/LO/1657). The study’s findings will be published in peer-reviewed journals and disseminated at national and international conferences. Trial Registration: ClinicalTrials.gov Identifier Number NCT02855255; ISRCTN registration number: ISRCTN23584477.

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STRENGTHS AND LIMITATIONS Strengths • This study adopted a Blinded Randomised Controlled Trial design • Chemical verification of quit success • Comparison of two common smoking cessation interventions Limitations • No ‘no treatment’ control • Although researchers are blinded, therapists delivering the interventions are not blinded i.e. each intervention is delivered by experienced facilitators for NHS and ACE separately.

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INTRODUCTION Dependence on nicotine has long been a problem and although statistics from the World Health Organization (1) show that the prevalence of tobacco smoking is declining worldwide, there are still a significant number of people, 1.1 billion in 2015, who continue to smoke (1) Smoking is a major cause of ill health and is associated with several diseases including cancer, coronary heart disease, and stroke. In the UK alone in 2014, there were 9.6 million smokers, with 78,000 deaths attributed to smoking (2). Many smokers want to quit and often make several attempts to do so, but the majority fail due to both physiological and psychological factors (3). Over the years, researchers have sought to develop effective cessation treatments in an effort to provide education and support. Consequently, many psychological and pharmacological treatments are available to help smokers quit, and although these types of intervention are undoubtedly the most costeffective interventions available (4), many people fail to maintain smoking cessation in the longer term (5). In 2014, it was reported that 37% of smokers made an attempt to quit but only 19% were actually successful (6).

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It is important to understand the relative efficacies of various interventions designed to help people quit, and recently NICE called for comparative studies to determine the short- and long-term effectiveness of Allen Carr's Easyway (ACE) method of stopping smoking. Whilst the ACE programme is well-established and its efficacy has received some empirical support (see Dijkstra et al. [7]), there has not to date been a randomised control trial testing the efficacy of this programme. Consequently, Allen Carr's Easyway to stop smoking and a 1-1 counselling service available via the NHS will be compared. By comparing the ACE program to a NHS delivered treatment program, an estimate of the relative effectiveness of ACE in comparison to the NHS service can be made. This will potentially inform future judgements about the use of this method by private and public health care providers. The findings will add to the evidence base around the use of the NHS stop smoking service and the Allen Carr’s Easyway method.

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METHODS/DESIGN Design

A two-arm, parallel-group, blinded1, randomised controlled trial.

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Treatment setting/site All intervention sessions for the NHS and ACE programmes will be delivered on the London South Bank University (LSBU) Southwark campus and the Allen Carr’s Easyway site in London, SW20. They begin in February 2017 and will run for eight months. 1

With researchers blind to participant condition, and participants blind to the condition they are not assigned to


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Study population People who smoke tobacco cigarettes and are motivated to quit. Inclusion and exclusion criteria Participants will be eligible provided they are at least 18 years of age, are current smokers who intend to quit and are prepared to be assigned randomly to one of two treatment conditions. Individuals who, on being asked at the point of recruitment would prefer an NHS provided treatment, are currently in another RCT or similar research project, disclose that they have a mental health condition, are pregnant or have a respiratory disease such as chronic obstructive pulmonary disease or emphysema will be excluded. Additionally, individuals who feel they are unable to reach the treatment location (London South Bank University’s Southwark Campus or London SW20) for treatment and follow-up will also be excluded.

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Interventions

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Allen Carr’s Easyway programme. The ACE intervention involves a single group session with up to 25 attendees, led by a trained facilitator. The five to six-hour session broadly comprises elements of CBT and ends with a short hypnotherapy/relaxation exercise. Participants are encouraged to carry on smoking as normal right up until they attend the clinic and during the session are encouraged to smoke as normal during scheduled smoking breaks (around every 45-60 minutes). Participants are assisted in identifying positive expectancies they associate with smoking (e.g. pleasure, support, crutch, or other benefits) before working towards the conclusion that the belief that smoking provides these benefits is, in fact, erroneous and harmful. Participants also achieve a basic understanding of how the psychological and pharmacological mechanisms of nicotine addiction facilitate the maintenance of erroneous and problematic beliefs. These sessions end with a ‘ritual’ final cigarette followed by an approximately 20-minute period of hypnotherapy – a light relaxation exercise that reinforces the main points of the session. At the end of each session each participant is asked to make a written record of what it was about their life as a smoker that made them want to stop. Following each session, the clinical team will call, email, or SMS text the participant on day 1, and again at 3, 7, 10, 14, 21, 30, 45, 60, 75, and 90 days with a short courtesy message such as “Hope you’re well. Please don’t hesitate to get in touch if you have any questions at all”, “Hope all is well with you. Don’t forget we’re here if you have any questions”.

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NHS smoking cessation programme. The NHS intervention comprises the NHS stop smoking service currently offered at Guy’s and St Thomas’ NHS Foundation Trust and Lambeth Public Health. This constitutes a single session of around 30 minutes which combines motivational interviewing and CBT, followed by four follow-up sessions. The initial session involves informing the client about the treatment programme, assessing current smoking, readiness to quit and past quit attempts. Participants are then advised on the operation of nicotine 4 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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dependence, the mechanics of withdrawal, and given advice on changing routine. The use, pros and cons of various Nicotine Replacement Therapies (NRTs) are also outlined. A quit date is set (within two weeks of receiving the intervention) and the importance of complete abstinence discussed. Finally, a carbon monoxide test is administered, and explained. Before the session finishes, participants are assisted in identifying high risk situations in the coming week, and develop quit action plans. This treatment is combined with prescribed NRT of the patients’ choice (including Varenicline). One, two and three weeks’ post quit date, shorter meetings (approximately 10 minutes) are arranged. These involve a progress check, a discussion around withdrawal symptoms and coping, a check on NRT supplies, a reflection on difficult situations encountered, a carbon monoxide test and planning for high risk situations in the coming week. The importance of abstinence is finally reinforced. Four weeks after the quit date, an approximately 10minute meeting checks on progress, measures carbon monoxide, advises on continued use of medication, discusses craving and urges and difficult situations and finally reinforces the importance of complete abstinence.

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Top-ups and Resets. Both treatments contain as standard, options to reset/top up quit dates. The ACE provision includes the option for clients to ‘top-up’ their treatment in two further sessions. These second and third sessions broadly follow the same format (approximately 3.5 hours) but contain more interaction and a smaller group (up to 15 clients) and can be carried out face-to-face or online. They can take place up to three months from the initial session. The clinician will provide contact details through which these sessions can be arranged. Should these optional sessions be taken up by a participant then the use of a top-up, and the date will be recorded by the clinician on the participant schedule and the subsequent testing dates will be based on the reset date. The primary outcome will be counted from the reset date (e.g. prior cigarettes consumed up to that point will be disregarded). The NHS arm contains the option for participants to be given a chance to reset their quit date, at the discretion and suggestion of the clinician. Should a reset be offered, the use of a reset and the revised date will be recorded, and the subsequent testing dates will be based on the reset date. The primary outcome will be counted from the reset date (i.e. prior cigarettes consumed up to that point will be disregarded).

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Both NHS and ACE treatments offer top-ups are part of treatment as usual, so it is reasonable that the smoke-free period starts from the date of the top-up (the top-up is part of the normal ‘dosage’ of the method). Therefore, all participants will have to be smoke-free for six months (primary outcome), in line with Russell 6 Standard, from the point they receive the treatment. People who do not slip more than the defined number of times, do not attend top-ups, and still maintain from the end of treatment to the final outcome point can of course self-recover. Where participants engage in a subsequent data collection point (i.e. 4 weeks) before top-up, this data will be held, but a new set of data will be collected and used in subsequent analysis.


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An alternative approach would be to track all participants from the end of a pre-specified ‘grace period’ which would allow for spontaneous resets. However, such a response would effectively mean that the actual smoke free period between end of treatment and the primary outcome measure point could vary considerably. If there are differences in the number of resets/top-ups used between treatment arms, this would introduce non-trivial systematic bias into the final analysis. In order to explore how the use of top-ups/resets affects outcomes, we will undertake secondary analysis looking only at those who did not use resets/top-ups (and, if appropriate in terms of statistical power, comparing rates between those that do and do not between arms).

Figure 1. Process diagram

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Outcomes

Primary Outcome Measures. The primary outcome for the trial is the proportion of participants who maintain sustained abstinence for 26 weeks after their quit date. Abstinence is defined using the Russell 6 Standard (i.e. fewer than 5 incidents of smoking from the quit date, including all participants lost to follow-up as failed treatment, and confirming all successful quits via breath carbon monoxide testing). The intention to treat principle will be followed, and those lost to follow-up will be considered as a failed quit (8).

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Secondary Outcome Measures. The following secondary outcome measures are being assessed in all participants at 4, 12 and 26 weeks post quit date: Self-reported maintenance of smoking cessation: measured by current cessation, number of cigarettes in past week/month/since last session; Use of Nicotine replacement therapy/nicotine containing products: Participants will be asked to answer Yes/No to the following: 'Since we last met, have you regularly used any of the following?' and 'Are you planning on using any of the following in the future?' E-cigarettes, Nicotine Patches, Nicotine Gum, Other; Perceived value of being nicotine free: measured on a scale of 1-7 (strongly disagree - strongly agree) to the following items: 'Being nicotine free is of value to me', 'I value being nicotine free', 'Having no nicotine in my system is / would be beneficial to me'; Satisfaction with Life (9): A well-validated 5-item scale designed to measure global cognitive judgements of one's life satisfaction. Participants indicate how much they agree or disagree with each of the 5-items using a scale of 1-7 (strongly disagree - strongly agree); Quit efficacy: measured on a scale of 1-7 (strongly disagree - strongly agree) to the following items: 'I can achieve my aims to quit smoking', 'I can cope with the demands of quitting smoking', 'It is unlikely that I will do well at quitting smoking', 'I think I can perform well at quitting smoking'. Readiness to change smoking behaviour (10): A well-validated measure of readiness to consider smoking cessation. Measured on a scale of 1 (lowest level of readiness) to 10 (highest level of readiness). Responses 1-3 are indicative of no plans to quit smoking, 4-6 range from thinking about quitting to planning to quit in the next six months, and 7-10 range from planning to quit in the next 30 days to having already quit smoking. Adverse events: Information regarding any adverse events relating to the participant’s health and wellbeing and whether they are related to treatment.

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Sample size Tests are powered to detect superiority. Based on data from Dijkstra et al. (7), an attrition rate between recruitment and final follow up (at 6 months) of 30% is indicated. To ensure sufficient participants in the final sample at this rate, an initial sample of 620 participants will be sought (310 per intervention group). To detect differences in success rates (at 6 months) in treatments with success rates of 30% and 50% respectively (powered at .95, alpha 0.05, and adjusting to account for a 25% loss to follow up) a sample size of 480 would be required. To detect differences between 20% and 40% quit rates (with the same assumptions) a sample of 400 would be required. To detect differences between 50% and 70% a sample size of 566 is needed. Thus, the study will be adequately powered to detect meaningful differences in the expected range, with loss to follow up rates in the region of previous research or somewhat above.

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Recruitment

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People will be informed of the trial through local placement of posters, leaflets to residential properties, booklets to major employers, employment networks and councils, webpages at LSBU, social media campaigns and radio advertisements. People interested in enrolling will be invited to contact London South Bank University to provide contact details and will be sent (via email or post) an information sheet containing written information about the study. Within two days, potential participants will be contacted by phone and undergo eligibility pre-screening. At this point they will not be informed which two interventions are being compared in the study. If eligible, participants will be asked about demographics, nicotine dependence and prior quit attempts to allow for stratified randomisation into the trial. Within two days of being screened the research team will send eligible participants a consent form (via post or email). As this stage is before intention to treat or condition allocation, no restrictions on contact attempts are placed on this stage. On gaining written consent, participant’s details will be sent to the independent randomiser for allocation. Once randomised, participants will see the research team four times (baseline, 4 weeks, 12 weeks and 26 weeks). They will be paid £15 cash for attending each measurement point and regardless of quit outcome, they will be entered into a prize draw to win a Caribbean holiday for two, an iPad or gym membership.

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Randomisation, allocation concealment and sequence generation Participants will be randomised to condition by Sarah White (study statistician) using the Kang and Park (11) ‘Covariate Adaptive Randomization Program’ (Version 1.0) software package. Four stratification factors, each at two levels, will be used: nicotine dependence (determined by the Fagerstrom Test for Nicotine Dependence [FTND] questionnaire (12)), number of prior quit attempts, age and gender. Participants will be assigned to the ACE and NHS 1-1 intervention groups in a ratio of 1.1 (310 in each).


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Blinding Participants will be blind to both interventions until randomised and once allocated will be blind to the alternative intervention. Members of the trial steering committee, management committee, and other team members (with the exception of the statistician/randomiser), will remain blind to treatment allocation until the last follow-up is completed and the data recorded, and the clinical team is not authorised to reveal it. Data collection, management and analysis All data will be collected via paper questionnaires, apart from carbon monoxide readings where a Smokerlyzer piCO analyser will be used. Participant data will be entered by the research team and will only be linked directly with their participant ID code. Personal data (e.g. identifiable data) will be accessible to the research team (as part of the screening process), the statistician and the direct care team. Hard copies of data will be destroyed via confidential waste disposal five years after the research findings have been published. Electronic copies of data will be stored in two archives. In both cases, only anonymous data will be archived. They will be archived at London South Bank Data Archive and a national data repository such as the UK Data Archive. For more information about data management and monitoring, please see the study research protocol. Statistical analyses

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A senior statistician determined the sample size and wrote the statistical analysis plan which was subsequently agreed by the Steering committee. All statistical analyses will be performed using SPSS version 24 software. Participants will be analysed on an intention to treat basis at the point of randomisation. 95% confidence intervals will be presented for all analyses. Missing data will be replaced by the mean within condition score. The following

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stratification variables will be included as covariates in all regression models: baseline quit efficacy (at inclusion), age (at inclusion), gender and baseline nicotine dependency. These covariates have been selected as they have been shown to influence treatment success, and we wish to investigate the unique effects of treatment across a demographically heterogeneous sample.

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Primary outcome analysis. Participants for whom smoking cessation cannot be confirmed (i.e. are lost to follow-up) will be included in the analysis as failed quits, in line with the Russell 6 Standard. Logistic regression will be used to estimate the effectiveness of the treatment condition upon smoking cessation at six months. A series of sensitivity analyses will be conducted to assess the robustness of primary results with regards to definition of the primary outcome. To investigate if the differential effects of interventions are present at each time point (4 and 12 weeks), the primary analysis will be repeated twice, the dependent variable being smoking cessation confirmed at 4 and 12 weeks. The primary analysis will be repeated on smoking cessation outcomes at both 12 and 26 weeks using only participants who did not ‘reset’ their quit dates (NHS arm) or attended 8 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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a top-up session (ACE arm). This is preferable to including them as failed quits, as many may in fact be successful cessations, whilst also attending a top-up. Secondary smoking outcomes. Use of NRT in each treatment arm will be tested by conducting a logistic regression. Treatment arm and treatment success will be included as the independent variables. Secondary non-smoking outcomes analyses. To analyse the take up of treatment between conditions, a logistic regression will be undertaken on treatment completion (operationalised as attendance at the ACE session and attendance at all five weeks of the NHS sessions). Multi-level regression models with time of measurement (4 weeks, 12 weeks and 26 weeks) will be undertaken with perceived value of being nicotine free, readiness to change, intentions to reengage, life satisfaction as the dependent variables, treatment arm as independent variable. Planned comparisons between treatment arms at each time point will be undertaken.

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Plan of presentation. A CONSORT diagram will be used to describe the sampling, drop-outs and randomisation. Funding

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This trial is funded in full by Allen Carr’s Easyway (International) Ltd. The NHS smoking cessation intervention is provided by Lambeth Stop Smoking Service. The design, conduct, data collection, analyses and interpretation of the trial are conducted by LSBU, independent from Allen Carr’s Easyway (International) Ltd. Based on the findings, papers for publication will be prepared by the research team at LSBU who will have ultimate authority over these activities.

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The research team are contractually free to publish whatever findings the study produces, ACE has no veto over publication, but will be given advanced notice of the findings prior to publication.

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Contributors 2 Ethics and Dissemination:

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This protocol has been independently peer reviewed by Professor Robert West, University College London and meets requirements of London - Fulham Research Ethics Committee, reference number 16/LO/1657. In addition, this protocol has been reviewed and approved by the Research Ethics Committee at London South Bank University. 2

DF, IA and AM conceived the design of the trial and secured funding. DF wrote the study protocol. KVW manages the day to day running of the trial. SW will undertake all data analyses. This protocol paper was written by KVW with input from all co-authors. DF is guarantor for this paper. All authors read and approved the final manuscript.


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Informed consent: Informed written consent will be obtained by the research team. Participants will be sent an information sheet containing information about the study and eligible participants will be required to provide informed written consent form before being randomised. At the end of the study, a non-technical summary of the results will be prepared for participants. The study findings will be disseminated through national and international conference presentations and will be reported in peer-reviewed journals. Competing interest: No Authors have any conflicts of interest with NHS stop smoking services, or Allen Carr’s Easyway to declare. The authors have no financial relationship or interest with the funding organisation.

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Acknowledgements: We would like to acknowledge Lambeth Public health for their support with this study. Data sharing statement: Electronic copies of data will be stored in two archives. In both cases, only anonymous data will be archived. They will be archived at:

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1) London South Bank University Data Archive. This is a secure repository hosted at the data centre at the University of London Computer Centre. This data will be available to academics and interested parties on request, with such access not being unreasonably withheld 2) A national data repository such as the UK Data Archive. This is an established national archive on secure servers. Researchers, students and teachers from any field, organisation or country may register with the UK Data Service and obtain data.

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Manuscript reporting: SPIRIT guidelines were followed when preparing this protocol

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Figure 1. Process diagram indicating the flow of participants through the study REFERENCES

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1. World Health Organisation. Global report on trends in prevalence of tobacco smoking.2015.http://www.who.int/tobacco/publications/surveillance/reportontren dstobaccosmoking/en/. 2. Health and Social Care Information Centre. Statistics on smoking. 2016. http://content.digital.nhs.uk/catalogue/PUB20781/stat-smok-eng-2016-rep.pdf 3. Bucchalter, A.R., Acosta, M.C., Evans, S.E., Breland, A.B., & Eissenberg, T. (2015). Tobacco abstinence symptom suppression: the role played by the smoking-related stimuli that are delivered by denicotinized cigarettes. Addiction, 100, 550-559. 4. Ronckers, E.T., Groot, W., & Ament, A.J. (2005). Systematic review of economic evaluations of smoking cessation: standardizing the cost-effectiveness. Medical Decision Making, 25, 437-448.

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5. Stead, L.F., Perera, R., Bullen, C., Mant, D., Hartmann-Boyce, J., Cahill, K., & Lancaster, T. (2012). Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews, 11. Art. No.: CD000146. Doi:10.1002/14651858.CD000146.pub4. 6. Public Health England (2016). Health matters: Smoking and quitting in England. https://www.gov.uk/government/publications/health-matters-smoking-andquitting-in-england/smoking-and-quitting-in-england 7. Dijkstra, A., Zuidema, R., Vos., D., & van Kalken, M. (2014). The effectiveness of the Allen Carr smoking cessation training in companies tested in quasi experimental design. BMC Public Health, 14, 952. 8. West, J., Hajek, P., Stead, L., & Stapleton, J. (2005). Outcome criteria in smoking cessation trials: proposal for a common standard. Addiction, 100, 299-303. 9. Diener, E., Emmons, R.A., Larsen, R.J., & Griffin, S. (1985). The satisfaction with life scale. Journal of Personality Assessment, 49, 71-75. 10. Beiner, L., & Abrams, D.B. (1991). The Contemplation Ladder: validation of a measure of readiness to consider smoking cessation. Health Psychology, 10, 360-365. 11. Kang, M., Ragan, B.G., & Park, J-H. (2007). Issues in Outcomes Research: An Overview of Randomization Techniques for Clinical Trials. Journal of Athletic Training, 43, 215-221. 12. Heatherton, F., Kozlowski, L.T., Frecker, R.C., & Fagerstrom, K.O. (1991). The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. British Journal of Addiction, 86, 1119-27.

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Process diagram

Potential participant contacts the Research team by phone or email.

Research team allocates participant number

Research team screens by phone or email using screening packet No exclusion criteria but not in preparation phase. Two week delay and re-contact. Three attempts before screened out. With a ‘ did not complete eligibility screening’ outcome on screened out spreadsheet.

Screen out to NHS service via NHS clinical team. Note on screened out spreadsheet.

Meets exclusion criteria

Eligibility Eligible

Research team: secures participant consent and hands participant details (and stratification details) to randomisation allocator via screening packet. Notes date consent received and date screened in on participant schedule

Randomisation allocator: Randomises to condition using covariate adaptive randomisation method to condition A or B.

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IINTENTION TO TREAT FROM AT THIS POINT Notes date of randomisation on participant schedule Notes condition on participant condition sheet Notes an additional allocation on condition count sheet Sends message to account A or B with participant details

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Clinical team: Schedules treatment with participants from another email account. Three attempts to schedule treatment before participant recorded as LTF and entered onto screened out spreadsheet

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Prior to treatment makes an appointment for baseline on Baseline appointment sheet up to a week before treatment for WAVE 1.

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Notes date of quit date on participant schedule. For ACE this is the treatment date, for NHS, it is the agreed quit date, but within 2 weeks of the intervention.

Yes

Resets / Top-up?

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No

Reset is recorded on participant schedule, dates reset from that point

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Research team: Schedules follow up waves 2, 3 and 4 using data from the participant schedule


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SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents* Section/item

PageNo

Description

Administrative information Title

1

Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym

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Trial registration

2

Trial identifier and registry name. If not yet registered, name of intended registry

-

All items from the World Health Organization Trial Registration Data Set

Protocol version

-

Date and version identifier

Funding

8

Roles and responsibilities

1,9

Names, affiliations, and roles of protocol contributors

1

Name and contact information for the trial sponsor

8,9

Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities

-

Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint adjudication committee, data management team, and other individuals or groups overseeing the trial, if applicable (see Item 21a for data monitoring committee)

3

Description of research question and justification for undertaking the trial, including summary of relevant studies (published and unpublished) examining benefits and harms for each intervention

3

Explanation for choice of comparators

Objectives

3

Specific objectives or hypotheses

Trial design

3,7,8

Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group), allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)

Sources and types of financial, material, and other support

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Introduction Background and rationale

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Methods: Participants, interventions, and outcomes Study setting

3

Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained

Eligibility criteria

4

Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists)

Interventions

4,5

Interventions for each group with sufficient detail to allow replication, including how and when they will be administered

-

Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease)

-

Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests)

-

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Relevant concomitant care and interventions that are permitted or prohibited during the trial

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Outcomes

5,6

Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended

Participant timeline

See Time schedule of enrolment, interventions (including any run-ins and proto washouts), assessments, and visits for participants. A schematic col diagram is highly recommended (see Figure) for RCT resea rch

Sample size

7

Estimated number of participants needed to achieve study objectives and how it was determined, including clinical and statistical assumptions supporting any sample size calculations

Recruitment

7

Strategies for achieving adequate participant enrolment to reach target sample size

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Methods: Assignment of interventions (for controlled trials) Allocation:


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Sequence generation

7-8

Method of generating the allocation sequence (eg, computergenerated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions

Allocation concealment mechanism

7-8

Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned

Implementation 7-8

Blinding (masking)

Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions

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Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how

8

If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s allocated intervention during the trial

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Methods: Data collection, management, and analysis 5-8

Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol

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Data collection methods

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See Plans to promote participant retention and complete follow-up, proto including list of any outcome data to be collected for participants who col discontinue or deviate from intervention protocols for RCT resea rch

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Data management

8

Plans for data entry, coding, security, and storage, including any related processes to promote data quality (eg, double data entry; range checks for data values). Reference to where details of data management procedures can be found, if not in the protocol

Statistical methods

8-9

Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the statistical analysis plan can be found, if not in the protocol

8-9

Methods for any additional analyses (eg, subgroup and adjusted analyses)


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8-9

Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation)

Methods: Monitoring Data monitoring

Harms

Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed

8

Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial

8

Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct

8

Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor

Ethics and dissemination

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Auditing

8

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Research ethics approval

9-10

Plans for seeking research ethics committee/institutional review board (REC/IRB) approval

Protocol amendments

-

Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes, analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals, regulators)

Consent or assent

8

Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and how (see Item 32)

-

Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable

Confidentiality

8

How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial

Declaration of interests

10

Financial and other competing interests for principal investigators for the overall trial and each study site

Access to data

10

Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators

Ancillary and post-trial care

-

Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial participation

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Dissemination policy

9-10

Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals, the public, and other relevant groups (eg, via publication, reporting in results databases, or other data sharing arrangements), including any publication restrictions

9-10

Authorship eligibility guidelines and any intended use of professional writers

-

Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code

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*It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items. Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons “Attribution-NonCommercial-NoDerivs 3.0 Unported” license.

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