Jinshuo Li

Bespoke smoking cessation for people with severe mental ill health (SCIMITAR): a pilot randomised controlled trial

BACKGROUND People with severe mental ill health are three times more likely to smoke but typically do not access conventional smoking cessation services, contributing to widening health inequalities and reduced life expectancy. We aimed to pilot an intervention targeted at smokers with severe mental ill health and to test methods of recruitment, randomisation, and follow up before implementing a full trial. METHODS The Smoking Cessation Intervention for Severe Mental Ill Health Trial (SCIMITAR) is a pilot randomised controlled trial of a smoking cessation strategy designed specifically for people with severe mental ill health, to be delivered by mental health nurses and consisting of behavioural support and drugs, compared with a conventional smoking cessation service (ie, usual care). Adults (aged 18 years or older) with bipolar disorder or schizophrenia, who were current smokers, were recruited from NHS primary care and mental health settings in the UK (York, Scarborough, Hull, and Manchester). Eligible participants were randomly allocated to either usual care (control group) or usual care plus the bespoke smoking cessation strategy (intervention group). Randomisation was done via a central telephone system, with computer-generated random numbers. We could not mask participants, family doctors, and researchers to the treatment allocation. Our primary outcome was smoking status at 12 months, verified by carbon monoxide measurements or self-report. Only participants who provided an exhaled CO measurement or self-reported their smoking status at 12 months were included in the primary analysis. The trial is registered at ISRCTN.com, number ISRCTN79497236. FINDINGS Of 97 people recruited to the pilot study, 51 were randomly allocated to the control group and 46 were assigned to the intervention group. Participants engaged well with the bespoke smoking cessation strategy, but no individuals assigned to usual care accessed NHS smoking cessation services. At 12 months, 35 (69%) controls and 33 (72%) people assigned to the intervention group provided a CO measurement or self-reported their smoking status. Smoking cessation was highest among individuals who received the bespoke intervention (12/33 [36%] vs 8/35 [23%]; adjusted odds ratio 2·9, 95% CI 0·8-10·5). INTERPRETATION We have shown the feasibility of recruiting and randomising people with severe mental ill health in a trial of this nature. The level of engagement with a bespoke smoking cessation strategy was higher than with a conventional approach. The effectiveness and safety of a smoking cessation programme designed particularly for people with severe mental ill health should be tested in a fully powered randomised controlled trial. FUNDING National Institute of Health Research Health Technology Assessment Programme.

Systematic identification and treatment of smokers by hospital based cessation practitioners in a secondary care setting: cluster randomised controlled trial

Objectives To investigate the effectiveness of the systematic default provision of smoking cessation support to all adult smokers admitted to hospital, relative to usual care. Design Open, cluster randomised controlled trial. Setting Acute medical wards in one large teaching hospital in the United Kingdom. Participants 264 patients randomised to intervention and 229 to usual care; primary outcome data were available at four weeks for 260 and 224 patients, respectively. All adult smokers and recent ex-smokers able to give informed consent were eligible for entry into the study. Interventions The intervention comprised systematic smoking ascertainment and default provision of behavioural support and cessation pharmacotherapy for the duration of the hospital stay for all smokers and recent ex-smokers, with follow-up and referral to community services after discharge. Usual care comprised cessation support delivered at the initiative and discretion of clinical staff. All staff and patients were aware of group assignment. Main outcome measures Smoking cessation at four weeks, validated by measuring exhaled carbon monoxide. Secondary outcomes were uptake of inpatient behavioural support, use of cessation pharmacotherapy, referral to and uptake of community support after discharge, and validated smoking cessation at six months. Participants lost to follow-up were assumed to have reverted to smoking. Results All patients in the intervention group received at least brief advice to quit smoking, compared to 106 (46%) patients in the usual care group. Cessation at four weeks was achieved by 38% (n=98) of intervention patients and 17% (n=37) of usual care patients (adjusted odds ratio 2.10 (95% confidence interval 0.96 to 4.61), P=0.06, number of patients needed to treat 8). Uptake of inpatient behavioural support, use of pharmacotherapy, and referral to and uptake of community support after discharge were all substantially and statistically significantly higher in the intervention group than in the usual care group. Cessation at six months was achieved by 19% (n=47) of intervention and 9% (n=19) of usual care patients, although this difference was not significant (adjusted odds ratio 1.53 (95% confidence interval 0.60 to 3.91); P=0.37). Conclusions Substantial improvements in smoking cessation among smokers admitted to hospital can be achieved by systematic ascertainment and delivery of cessation support in secondary care. Trial registration International Standard Randomised Controlled Trial Number ISRCTN25441641.

Smoking Cessation Intervention for severe Mental Ill Health Trial (SCIMITAR): a pilot randomised control trial of the clinical effectiveness and cost-effectiveness of a bespoke smoking cessation service

BACKGROUND There is a high prevalence of smoking among people who experience severe mental ill health (SMI). Helping people with disorders such as bipolar illness and schizophrenia to quit smoking would help improve their health, increase longevity and also reduce health inequalities. Around half of people with SMI who smoke express an interest in cutting down or quitting smoking. There is limited evidence that smoking cessation can be achieved for people with SMI. Those with SMI rarely access routine NHS smoking cessation services. This suggests the need to develop and evaluate a behavioural support and medication package tailored to the needs of people with SMI. OBJECTIVE The objective in this project was to conduct a pilot trial to establish acceptability of the intervention and to ensure the feasibility of recruitment, randomisation and follow-up. We also sought preliminary estimates of effect size in order to design a fully powered trial of clinical effectiveness and cost-effectiveness. The pilot should inform a fully powered trial to compare the clinical effectiveness and cost-effectiveness of a bespoke smoking cessation (BSC) intervention with usual general practitioner (GP) care for people with SMI. DESIGN A pilot pragmatic two-arm individually randomised controlled trial (RCT). Simple randomisation was used following a computer-generated random number sequence. Participants and practitioners were not blinded to allocation. SETTING Primary care and secondary care mental health services in England. PARTICIPANTS Smokers aged > 18 years with a severe mental illness who would like to cut down or quit smoking. INTERVENTIONS A BSC intervention delivered by mental health specialists trained to deliver evidence-supported smoking cessation interventions compared with usual GP care. MAIN OUTCOME MEASURES The primary outcome was carbon monoxide-verified smoking cessation at 12 months. Smoking-related secondary outcomes were reduction of number of cigarettes smoked, Fagerstrom test of nicotine dependence and motivation to quit (MTQ). Other secondary outcomes were Patient Health Questionnaire-9 items and Short Form Questionnaire-12 items to assess whether there were improvements or deterioration in mental health and quality of life. We also measured body mass index to assess whether or not smoking cessation was associated with weight gain. These were measured at 1, 6 and 12 months post randomisation. RESULTS The trial recruited 97 people aged 19-73 years who smoked between 5 and 60 cigarettes per day (mean 25 cigarettes). Participants were recruited from four mental health trusts and 45 GP surgeries. Forty-six people were randomised to the BSC intervention and 51 people were randomised to usual GP care. The odds of quitting at 12 months was higher in the BSC intervention (36% vs. 23%) but did not reach statistical significance (odds ratio 2.9; 95% confidence interval 0.8% to 10.5%). At 3 and 6 months there was no evidence of difference in self-reported smoking cessation. There was a non-significant reduction in the number of cigarettes smoked and nicotine dependence. MTQ and number of quit attempts all increased in the BSC group compared with usual care. There was no difference in terms of quality of life at any time point, but there was evidence of an increase in depression scores at 12 months for the BSC group. There were no serious adverse events thought likely to be related to the trial interventions. The pilot economic analysis demonstrated that it was feasible to carry out a full economic analysis. CONCLUSIONS It was possible to recruit people with SMI from primary and secondary care to a trial of a smoking cessation intervention based around behavioural support and medication. The overall direction of effect was a positive trend in relation to biochemically verified smoking cessation and it was feasible to obtain follow-up in a substantial proportion of participants. A definitive trial of a bespoke cessation intervention has been prioritised by the National Institute for Health Research (NIHR) and the SCIMITAR pilot trial forms a template for a fully powered RCT to examine clinical effectiveness and cost-effectiveness. TRIAL REGISTRATION Current Controlled Trials ISRCTN79497236. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment, Vol. 19, No. 25. See the NIHR Journals Library website for further project information.

Web-based self-management support for people with type 2 diabetes (HeLP-Diabetes): randomised controlled trial in English primary care.

Objective To determine the effectiveness of a web-based self-management programme for people with type 2 diabetes in improving glycaemic control and reducing diabetes-related distress. Methods and design Individually randomised two-arm controlled trial. Setting 21 general practices in England. Participants Adults aged 18 or over with a diagnosis of type 2 diabetes registered with participating general practices. Intervention and comparator Usual care plus either Healthy Living for People with Diabetes (HeLP-Diabetes), an interactive, theoretically informed, web-based self-management programme or a simple, text-based website containing basic information only. Outcomes and data collection Joint primary outcomes were glycated haemoglobin (HbA1c) and diabetes-related distress, measured by the Problem Areas in Diabetes (PAID) scale, collected at 3 and 12 months after randomisation, with 12 months the primary outcome point. Research nurses, blind to allocation collected clinical data; participants completed self-report questionnaires online. Analysis The analysis compared groups as randomised (intention to treat) using a linear mixed effects model, adjusted for baseline data with multiple imputation of missing values. Results Of the 374 participants randomised between September 2013 and December 2014, 185 were allocated to the intervention and 189 to the control. Final (12 month) follow-up data for HbA1c were available for 318 (85%) and for PAID 337 (90%) of participants. Of these, 291 (78%) and 321 (86%) responses were recorded within the predefined window of 10–14 months. Participants in the intervention group had lower HbA1c than those in the control (mean difference −0.24%; 95% CI −0.44 to −0.049; p=0.014). There was no significant overall difference between groups in the mean PAID score (p=0.21), but prespecified subgroup analysis of participants who had been more recently diagnosed with diabetes showed a beneficial impact of the intervention in this group (p = 0.004). There were no reported harms. Conclusions Access to HeLP-Diabetes improved glycaemic control over 12 months. Trial registration number ISRCTN02123133.

ADAPTA: A pilot randomised controlled trial of an alcohol-focused intervention versus a healthy living intervention for problem drinkers identified in a general hospital setting

Highlights • No evidence of a difference in AUDIT score was seen between treatments at 6 months.• A greater proportion in the healthy living group attended all 4 treatment sessions.• Recruitment and follow up proved challenging with this non-help seeking group.• Further thought needed regarding engaging problem drinkers in a hospital setting.

Cost-Effectiveness of Nicotine Patches for Smoking Cessation in Pregnancy: A Placebo Randomized Controlled Trial (SNAP)

INTRODUCTION Smoking during pregnancy is the most important, preventable cause of adverse pregnancy outcomes including miscarriage, premature birth, and low birth weight with huge financial costs to the National Health Service. However, there are very few published economic evaluations of smoking cessation interventions in pregnancy and previous studies are predominantly U.S.-based and do not present incremental cost-effectiveness ratios (ICER). A number of studies have demonstrated cost-effectiveness of nicotine replacement therapy (NRT) in the general population, but this has yet to be tested among pregnant smokers. METHODS A cost-effectiveness analysis was undertaken alongside the smoking, nicotine, and pregnancy trial to compare NRT patches plus behavioral support to behavioral support alone, for pregnant women who smoked. RESULTS At delivery, biochemically verified quit rates were slightly higher at 9.4% in the NRT group compared to 7.6% in the control group (odds ratio = 1.26, 95% CI = 0.82-1.96), at an increased cost of around £90 per participant. Higher costs in the NRT group were mainly attributable to the cost of NRT patches (mean = £46.07). The incremental cost-effectiveness ratio associated with NRT was £4,926 per quitter and a sensitivity analysis including only singleton births yielded an ICER of £4,156 per quitter. However, wide confidence intervals indicated a high level of uncertainty. CONCLUSIONS Without a specific willingness to pay threshold, and due to high levels of statistical uncertainty, it is hard to determine the cost-effectiveness of NRT in this population. Furthermore, future research should address compliance issues, as these may dilute any potential effects of NRT, thus reducing the cost-effectiveness.

Youth social behaviour and network therapy (Y-SBNT): adaptation of a family and social network intervention for young people who misuse alcohol and drugs - a randomised controlled feasibility trial.

BACKGROUND Family interventions appear to be effective at treating young peoples substance misuse. However, implementation of family approaches in UK services is low. This study aimed to demonstrate the feasibility of recruiting young people to an intervention based on an adaptation of adult social behaviour and network therapy. It also sought to involve young people with experience of using substance misuse services in the research process. OBJECTIVES To demonstrate the feasibility of recruiting young people to family and social network therapy and to explore ways in which young people with experience of using substance misuse services could be involved in a study of this nature. DESIGN A pragmatic, two-armed, randomised controlled open feasibility trial. SETTING Two UK-based treatment services for young people with substance use problems, with recruitment taking place from May to November 2014. PARTICIPANTS Young people aged 12-18 years, newly referred and accepted for structured interventions for drug and/or alcohol problems. INTERVENTIONS A remote, web-based computer randomisation system allocated young people to adapted youth social behaviour and network therapy (Y-SBNT) or treatment as usual (TAU). Y-SBNT participants were intended to receive up to six 50-minute sessions over a maximum of 12 weeks. TAU participants continued to receive usual care delivered by their service. MAIN OUTCOME MEASURES Feasibility was measured by recruitment rates, retention in treatment and follow-up completion rates. The main clinical outcome was the proportion of days on which the main problem substance was used in the preceding 90-day period as captured by the Timeline Follow-Back interview at 3 and 12 months. RESULTS In total, 53 young people were randomised (Y-SBNT, n = 26; TAU, n = 27) against a target of 60 (88.3%). Forty-two young people attended at least one treatment session [Y-SBNT 22/26 (84.6%); TAU 20/27 (74.1%)]; follow-up rates were 77.4% at month 3 and 73.6% at month 12. Data for nine young people were missing at both months 3 and 12, so the main clinical outcome analysis was based on 24 young people (92.3%) in the Y-SBNT group and 20 young people (74.1%) in the TAU group. At month 12, the average proportion of days that the main problem substance was used in the preceding 90 days was higher in the Y-SBNT group than in the TAU group (0.54 vs. 0.41; adjusted mean difference 0.13, 95% confidence interval -0.12 to 0.39; p = 0.30). No adverse events were reported. Seventeen young people with experience of substance misuse services were actively involved throughout the study. They informed key elements of the intervention and research process, ensuring that the intervention was acceptable and relevant to our target groups; contributing to the design of key trial documents, ideas for a new model of public involvement and this report. Two parents were also involved. CONCLUSIONS The adapted intervention could be delivered in young peoples services, and qualitative interviews found that Y-SBNT was acceptable to young people, family members and staff. Engagement of family and network members proved difficult within the intervention and research aspects. The study proved the feasibility of this work in routine services but outcome measurement based on narrow substance use variables may be limited and may fail to capture other important changes in wider areas of functioning for young people. Validation of the EuroQol-5 Dimensions for young people aged 12-18 years should be considered and flexible models for involvement of young people in research are required to achieve inclusive representation throughout all aspects of the research process. Although recommendation of a full trial of the Y-SBNT intervention compared with TAU is not supported, this study can inform future intervention development and UK research within routine addiction services. TRIAL REGISTRATION Current Controlled Trials ISRCTN93446265. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 15. See the NIHR Journals Library website for further project information.

Effectiveness of a mobile, drop-in stop smoking service in reaching and supporting disadvantaged UK smokers to quit

Background In countries where there are large disparities in smoking with persistent high rates among disadvantaged groups, there is a need to ensure that stop smoking services (SSS) reach such smokers. The primary aim of this study was to evaluate the effectiveness of a mobile, drop-in, community-based SSS in reaching more disadvantaged smokers, particularly those from routine and manual (RM) occupation groups, than standard services; secondary aims were to evaluate effectiveness in reaching those who had not previously accessed SSS, triggering unplanned quit behaviour, helping people quit and cost-effectiveness. Methods Following a 4-week pilot period, a mobile drop-in SSS was delivered across various public locations in Nottingham City, UK for 6 months, offering behavioural and pharmacological support via one-to-one consultations with trained cessation advisors. Detailed demographic and smoking behaviour data were collected from all clients accessing the mobile SSS, and Nottinghams standard SSS for comparison. Results Compared with smokers accessing the standard SSS (n=1856), mobile SSS smokers (n=811) were significantly more likely to be from the RM group (33.3% vs 27.2%, p=0.002), and to be first-time SSS users (67.8% vs 59.3%, p<0.001). Nearly 1 in 10 smokers setting a quit date through the mobile SSS had no prior quit intentions. The cost per smoker setting a quit date for the mobile SSS was only slightly higher than the standard SSS (£224 vs £202). Conclusions A mobile drop-in SSS is an effective way of reaching more disadvantaged smokers from RM occupations, as well as those who have not previously accessed standard SSS and those without prior quit intentions.

Cost-Effectiveness of Facilitated Access to a Self-Management Website, Compared to Usual Care, for Patients With Type 2 Diabetes (HeLP-Diabetes): Randomized Controlled Trial

Background Type 2 diabetes mellitus is one of the most common long-term conditions, and costs health services approximately 10% of their total budget. Active self-management by patients improves outcomes and reduces health service costs. While the existing evidence suggested that uptake of self-management education was low, the development of internet-based technology might improve the situation. Objective To establish the cost-effectiveness of a Web-based self-management program for people with type 2 diabetes (HeLP-Diabetes) compared to usual care. Methods An incremental cost-effectiveness analysis was conducted, from a National Health Service and personal and social services perspective, based on data collected from a multi-center, two-arm individually randomized controlled trial over 12 months. Adults aged 18 or over with a diagnosis of type 2 diabetes and registered with the 21 participating general practices (primary care) in England, UK, were approached. People who were unable to provide informed consent or to use the intervention, terminally ill, or currently participating in a trial of an alternative self-management intervention, were excluded. The participants were then randomized to either usual care plus HeLP-Diabetes, an interactive, theoretically-informed Web-based self-management program, or to usual care plus access to a comparator website containing basic information only. The participants’ intervention costs and wider health care resource use were collected as well as two health-related quality of life measures: the Problem Areas in Diabetes (PAID) Scale and EQ-5D-3L. EQ-5D-3L was then used to calculate quality-adjusted life years (QALYs). The primary analysis was based on intention-to-treat, using multiple imputation to handle the missing data. Results In total, 374 participants were randomized, with 185 in the intervention group and 189 in the control group. The primary analysis showed incremental cost-effectiveness ratios of £58 (95% CI –411 to 587) per unit improvement on PAID scale and £5550 (95% CI –21,077 to 52,356) per QALY gained by HeLP-Diabetes, compared to the control. The complete case analysis showed less cost-effectiveness and higher uncertainty with incremental cost-effectiveness ratios of £116 (95% CI –1299 to 1690) per unit improvement on PAID scale and £18,500 (95% CI –203,949 to 190,267) per QALY. The cost-effectiveness acceptability curve showed an 87% probability of cost-effectiveness at £20,000 per QALY willingness-to-pay threshold. The one-way sensitivity analyses estimated 363 users would be needed to use the intervention for it to become less costly than usual care. Conclusions Facilitated access to HeLP-Diabetes is cost-effective, compared to usual care, under the recommended threshold of £20,000 to £30,000 per QALY by National Institute of Health and Care Excellence. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN) 02123133; http://www.controlled-trials.com/ISRCTN02123133 (Archived by WebCite at http://www.webcitation.org/6zqjhmn00)

Nicotine preloading for smoking cessation: the Preloading RCT.

BACKGROUND Nicotine preloading means using nicotine replacement therapy prior to a quit date while smoking normally. The aim is to reduce the drive to smoke, thereby reducing cravings for smoking after quit day, which are the main cause of early relapse. A prior systematic review showed inconclusive and heterogeneous evidence that preloading was effective and little evidence of the mechanism of action, with no cost-effectiveness data. OBJECTIVES To assess (1) the effectiveness, safety and tolerability of nicotine preloading in a routine NHS setting relative to usual care, (2) the mechanisms of the action of preloading and (3) the cost-effectiveness of preloading. DESIGN Open-label randomised controlled trial with examination of mediation and a cost-effectiveness analysis. SETTING NHS smoking cessation clinics. PARTICIPANTS People seeking help to stop smoking. INTERVENTIONS Nicotine preloading comprised wearing a 21 mg/24 hour nicotine patch for 4 weeks prior to quit date. In addition, minimal behavioural support was provided to explain the intervention rationale and to support adherence. In the comparator group, participants received equivalent behavioural support. Randomisation was stratified by centre and concealed from investigators. MAIN OUTCOME MEASURES The primary outcome was 6-month prolonged abstinence assessed using the Russell Standard. The secondary outcomes were 4-week and 12-month abstinence. Adverse events (AEs) were assessed from baseline to 1 week after quit day. In a planned analysis, we adjusted for the use of varenicline (Champix®; Pfizer Inc., New York, NY, USA) as post-cessation medication. Cost-effectiveness analysis took a health-service perspective. The within-trial analysis assessed health-service costs during the 13 months of trial enrolment relative to the previous 6 months comparing trial arms. The base case was based on multiple imputation for missing cost data. We modelled long-term health outcomes of smoking-related diseases using the European-study on Quantifying Utility of Investment in Protection from Tobacco (EQUIPT) model. RESULTS In total, 1792 people were eligible and were enrolled in the study, with 893 randomised to the control group and 899 randomised to the intervention group. In the intervention group, 49 (5.5%) people discontinued preloading prematurely and most others used it daily. The primary outcome, biochemically validated 6-month abstinence, was achieved by 157 (17.5%) people in the intervention group and 129 (14.4%) people in the control group, a difference of 3.02 percentage points [95% confidence interval (CI) -0.37 to 6.41 percentage points; odds ratio (OR) 1.25, 95% CI 0.97 to 1.62; p = 0.081]. Adjusted for use of post-quit day varenicline, the OR was 1.34 (95% CI 1.03 to 1.73; p = 0.028). Secondary abstinence outcomes were similar. The OR for the occurrence of serious AEs was 1.12 (95% CI 0.42 to 3.03). Moderate-severity nausea occurred in an additional 4% of the preloading group compared with the control group. There was evidence that reduced urges to smoke and reduced smoke inhalation mediated the effect of preloading on abstinence. The incremental cost-effectiveness ratio at the 6-month follow-up for preloading relative to control was £710 (95% CI -£13,674 to £23,205), but preloading was dominant at 12 months and in the long term, with an 80% probability that it is cost saving. LIMITATIONS The open-label design could partially account for the mediation results. Outcome assessment could not be blinded but was biochemically verified. CONCLUSIONS Use of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can increase the proportion of people who stop successfully, but its benefit is undermined because it reduces the use of varenicline after preloading. If this latter effect could be overcome, then nicotine preloading appears to improve health and reduce health-service costs in the long term. Future work should determine how to ensure that people using nicotine preloading opt to use varenicline as cessation medication. TRIAL REGISTRATION Current Controlled Trials ISRCTN33031001. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 41. See the NIHR Journals Library website for further project information.