Cost-utility of cytisine for smoking cessation over and above behavioural support in people with newly diagnosed pulmonary tuberculosis: an economic evaluation of a multicentre randomised controlled trial.

OBJECTIVES: To assess the cost-effectiveness of cytisine over and above brief behavioural support (BS) for smoking cessation among patients who are newly diagnosed with pulmonary tuberculosis (TB) in low-income and middle-income countries. DESIGN: An incremental cost-utility analysis was undertaken alongside a 12-month, double-blind, two-arm, individually randomised controlled trial from a public/voluntary healthcare sector perspective with the primary endpoint at 6 months post randomisation. SETTING: Seventeen subdistrict hospitals in Bangladesh and 15 secondary care hospitals in Pakistan. PARTICIPANTS: Adults (aged ≥18 years in Bangladesh and ≥15 years in Pakistan) with pulmonary TB diagnosed within the last 4 weeks who smoked tobacco daily (n=2472). INTERVENTIONS: Two brief BS sessions with a trained TB health worker were offered to all participants. Participants in the intervention arm (n=1239) were given cytisine (25-day course) while those in the control arm (n=1233) were given placebo. No significant difference was found between arms in 6-month abstinence. PRIMARY AND SECONDARY OUTCOME MEASURES: Costs of cytisine and BS sessions were estimated based on research team records. TB treatment costs were estimated based on TB registry records. Additional smoking cessation and healthcare costs and EQ-5D-5L data were collected at baseline, 6-month and 12-month follow-ups. Costs were presented in purchasing power parity (PPP) adjusted US dollars (US$). Quality-adjusted life years (QALYs) were derived from the EQ-5D-5L. Incremental total costs and incremental QALYs were estimated using regressions adjusting for respective baseline values and other baseline covariates. Uncertainty was assessed using bootstrapping. RESULTS: Mean total costs were PPP US$57.74 (95% CI 49.40 to 83.36) higher in the cytisine arm than in the placebo arm while the mean QALYs were -0.001 (95% CI -0.004 to 0.002) lower over 6 months. The cytisine arm was dominated by the placebo arm. CONCLUSIONS: Cytisine plus BS for smoking cessation among patients with TB was not cost-effective compared with placebo plus BS. TRIAL REGISTRATION NUMBER: ISRCTN43811467.

Cytisine for smoking cessation in patients with tuberculosis: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan. METHODS: We did a randomised, double-blind, placebo-controlled, trial at 32 health centres in Bangladesh and Pakistan. Eligible patients were adults (aged >18 years in Bangladesh; aged >15 years in Pakistan) with pulmonary tuberculosis diagnosed in the previous 4 weeks, who smoked tobacco on a daily basis and were willing to stop smoking. Patients were randomly assigned (1:1) to receive behavioural support plus either oral cytisine (9 mg on day 0, which was gradually reduced to 1·5 mg by day 25) or placebo for 25 days. Randomisation was done using pregenerated block randomisation lists, stratified by trial sites. Investigators, clinicians, and patients were masked to treatment allocation. The primary outcome was continuous abstinence at 6 months, defined as self-report (of not having used more than five cigarettes, bidis, a water pipe, or smokeless tobacco products since the quit date), confirmed biochemically by a breath carbon monoxide reading of less than 10 parts per million. Primary and safety analysis were done in the intention-to-treat population. This trial is registered with the International Standard Randomised Clinical Trial Registry, ISRCTN43811467, and enrolment is complete. FINDINGS: Between June 6, 2017, and April 30, 2018, 2472 patients (1527 patients from Bangladesh; 945 patients from Pakistan) were enrolled and randomly assigned to receive cytisine (n=1239) or placebo (n=1233). At 6 months, 401 (32·4%) participants in the cytisine group and 366 (29·7%) participants in the placebo group had achieved continuous abstinence (risk difference 2·68%, 95% CI -0·96 to 6·33; relative risk 1·09, 95% CI 0·97 to 1·23, p=0·114). 53 (4·3%) of 1239 participants in the cytisine group and 46 (3·7%) of 1233 participants in the placebo group reported serious adverse events (94 events in the cytisine group and 90 events in the placebo group), which included 91 deaths (49 in the cytisine group and 42 in the placebo group). None of the adverse events were attributed to the study medication. INTERPRETATION: Our findings do not support the addition of cytisine to brief behavioural support for the treatment of tobacco dependence in patients with tuberculosis. FUNDING: European Union Horizon 2020 and Health Data Research UK. TRANSLATIONS: For the Bengali and Urdu translations of the abstract see Supplementary Materials section.

Prevalence of physical health conditions and health risk behaviours in people with severe mental illness in South Asia: protocol for a cross-sectional study (IMPACT SMI survey).

INTRODUCTION: People with severe mental illness (SMI) die on average 10-20 years earlier than the general population. Most of these deaths are due to physical health conditions. The aim of this cross-sectional study is to determine the prevalence of physical health conditions and their associations with health-risk behaviours, health-related quality of life and various demographic, behavioural, cognitive, psychological and social variables in people with SMI attending specialist mental health facilities in South Asia. METHODS AND ANALYSIS: We will conduct a survey of patients with SMI attending specialist mental health facilities in Bangladesh, India and Pakistan (n=4500). Diagnosis of SMI will be confirmed using the Mini-international neuropsychiatric interview V.6.0. We will collect information about physical health and related health-risk behaviours (WHO STEPwise approach to Surveillance (STEPS)); severity of common mental disorders (Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder scale (GAD-7)) and health-related quality of life (EQ-5D-5L). We will measure blood pressure, height, weight and waist circumference according to WHO guidelines. We will also measure glycated haemoglobin, lipid profile, thyroid function, liver function, creatinine and haemoglobin. Prevalence rates of physical health conditions and health-risk behaviours will be presented and compared with the WHO STEPS survey findings in the general population. Regression analyses will explore the association between health-risk behaviours, mental and physical health conditions. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of the Department of Health Sciences University of York (UK), Centre for Injury Prevention and Rehabilitation (Bangladesh), Health Ministry Screening Committee and Indian Council of Medical Research (India) and National Bioethics Committee (Pakistan). Findings will be disseminated in peer-reviewed articles, in local and international conferences and as reports for policymakers and stakeholders in the countries involved. TRIAL REGISTRATION NUMBER: ISRCTN88485933; 3 June 2019.

Varenicline versus placebo for waterpipe smoking cessation: a double-blind randomized controlled trial.

BACKGROUND AND AIMS: Waterpipe tobacco smoking is a growing public health concern. There is limited research using pharmacotherapy and no research using varenicline (established treatment for smoking cessation) in waterpipe smokers. We tested the efficacy of varenicline in achieving abstinence from all tobacco use among waterpipe smokers. DESIGN: Two-arm, parallel group, placebo-controlled, double-blind, multi-centre (n = 4), individually randomized trial with follow-up to 25 weeks. SETTINGS: District general hospitals and catchment communities within four districts of Punjab, Pakistan. PARTICIPANTS: Adult daily waterpipe smokers (n = 510; 253 in varenicline and 257 in placebo arms), who were interested in quitting, were recruited and analysed between March and November 2016. Of these, 220 (87%) in the varenicline and 239 (93%) in the placebo arms completed all follow-ups. Participants were on average aged 49 [standard deviation (SD) = 15.2] years, daily smokers and smoked for the last 27 (SD = 15.9) years. More than half (261, 51.2%) also smoked cigarettes. INTERVENTION AND COMPARATOR: All trial participants received two structured sessions of behavioural support (of 30 and 10 minutes) one at the time of registration and the other 1 week later. Participants were randomized to varenicline (active arm) and placebo (control arm) stratified on district, sex and concomitant cigarette smoking. Varenicline and placebo were dispensed as identical unlabelled tablets for 12 weeks: 0.5 mg for 1 week (once on days 1-3, twice on days 4-7) and 1 mg for the subsequent 11 weeks (twice daily). MEASUREMENTS: The trial participants were followed-up for a period of 25 weeks post-randomization. The primary outcome was 7-day repeated point prevalence abstinence from all forms of tobacco, self-reported at each of weeks 5, 12 and 25, verified by carbon-monoxide cut-off < 10 parts per million. FINDINGS: No evidence of statistically significant difference in repeated point prevalence abstinence between the varenicline (12 of 253; 4.7%) and placebo (11 of 257; 4.3%) arms (relative risk = 1.11, 95% confidence interval = 0.50-2.47, P = 0.80) was observed (Bayes factor = 0.048). Adverse events reported in 27 participants were 34 (15 in varenicline and 19 in placebo); none was serious. CONCLUSIONS: Varenicline was not more effective than placebo in aiding cessation of tobacco use in long-term daily waterpipe smokers.

The efficacy of varenicline in achieving abstinence among waterpipe tobacco smokers - study protocol for a randomized controlled trial.

BACKGROUND: Waterpipe tobacco smoking has increased among youth across the globe including in the US, and it continues as a common and traditional form of smoking tobacco in Pakistan. A range of behavioral and pharmacological therapies are available to support people in quitting cigarette smoking; however, little evidence exists for the efficacy of these therapies in achieving abstinence among waterpipe tobacco smokers. The objective of this study is to assess the efficacy of varenicline when added to behavioral support for waterpipe tobacco smoking cessation, by measuring biochemically validated continuous abstinence in waterpipe tobacco smokers. METHODS/DESIGN: This is a two-arm, double-blind, placebo-controlled randomized trial conducted in four districts in Punjab, Pakistan. Study participants include adults using a waterpipe (with or without concomitant cigarette, bidi or other forms of tobacco smoking) on a daily basis for at least 6 months and who are willing to quit. We will individually randomize 510 participants to one of the two arms of the trial. Participants in the intervention arm will receive varenicline and behavioral support and those in the control arm will receive placebo and behavioral support. The primary outcome will be continuous abstinence for at least 6 months (week 25) which is biochemically verified by a carbon monoxide level of <10 ppm. Secondary outcomes will include biochemically verified 7-day point abstinence at 5, 12 and 25 weeks and any lapses and relapses between the different assessment points. Tertiary outcomes will include assessment of withdrawal symptoms using the Mood and Physical Symptoms Scale (MPSS), smoking dependency using the Lebanon Waterpipe Dependency Scale (LWDS-11) and monitoring adverse outcomes. DISCUSSION: This is an efficacy trial and would require a subsequent effectiveness trial for a definitive evaluation of the intervention. TRIAL REGISTRATION: ISRCTN, ISRCTN94103375 . Registered on 1 December 2015.