The effectiveness, safety and cost-effectiveness of cytisine versus varenicline for smoking cessation in an Australian population: a study protocol for a randomized controlled non-inferiority trial

Smoking cessation medications are effective but often underutilised because of costs and side effects. Cytisine is a plant-based smoking cessation medication with over 50 years of use in Central and Eastern Europe. While cytisine has been found to be well-tolerated and more effective than nicotine replacement therapy, direct comparison with varenicline have not been conducted. This study evaluates the effectiveness, safety and cost-effectiveness of cytisine compared with varenicline.Two arm, parallel group, randomised, non-inferiority trial, with allocation concealment and blinded outcome assessment.Australian population-based study.Adult daily smokers (N=1266) interested in quitting will be recruited through advertisements and Quitline telephone-based cessation support services.Eligible participants will be randomised (1:1 ratio) to receive either cytisine capsules (25-day supply) or varenicline tablets (12-week supply), prescribed in accordance with the manufacturer's recommended dosing regimen. The medication will be mailed to each participant's nominated residential address. All participants will also be offered standard Quitline behavioural support (up to six 10-12 minute sessions).Assessments will be undertaken by telephone at baseline, 4- and 7-months post-randomisation. Participants will also be contacted twice (two and four weeks post-randomisation) to ascertain adverse events, treatment adherence and smoking status. The primary outcome will be self-reported 6-month continuous abstinence from smoking, verified by carbon monoxide at 7-month follow-up. We will also evaluate the relative safety and cost-effectiveness of cytisine compared with varenicline. Secondary outcomes will include self-reported continuous and 7-day point prevalence abstinence and cigarette consumption at each follow-up interview.If cytisine is as effective as varenicline, its lower cost and natural plant-based composition may make it an acceptable and affordable smoking cessation medication that could save millions of lives worldwide

Effectiveness, safety and cost-effectiveness of vaporized nicotine products versus nicotine replacement therapy for tobacco smoking cessation in a low-socioeconomic status Australian population: a study protocol for a randomized controlled trial

Background: In Australia, tobacco smoking rates have declined but inequalities remain with significantly higher smoking prevalence among low-socioeconomic populations. Clinical trial data suggest vaporized nicotine products (VNPs) aid smoking cessation. Most VNP trials have used refillable tank systems, but newer generation (pod) devices now comprise the largest market share yet have limited clinical trial evidence on safety and effectiveness. This study evaluates the effectiveness, safety and cost-effectiveness of VNPs (pod and tank device) compared with nicotine replacement therapy ([NRT]—gum or lozenge) for smoking cessation. Methods: This is a two-arm, open-label, superiority, parallel group, randomized controlled trial (RCT) with allocation concealment and blinded outcome assessment. The RCT is conducted at the National Drug and Alcohol Research Centre at the University of New South Wales, Sydney, Australia. Participants are people who smoke daily, are interested in quitting and receive a government pension or allowance (N = 1058). Participants will be randomized (1:1 ratio) to receive 8 weeks of free: VNPs, with pod (40 mg/mL nicotine salt) and tank device (18 mg/mL freebase nicotine) in mixed flavours; or NRT (gum or lozenge; 4 mg). All participants will receive daily text message behavioural support for 5 weeks. Assessments will be undertaken by telephone at baseline, with three follow-up calls (two check-in calls within the first month and final follow-up at 7 months post randomization) to ascertain smoking status, treatment adherence and adverse events. The primary outcome is 6-month continuous abstinence verified by carbon monoxide breath test of ≤5ppm at 7-month follow-up. Safety and cost-effectiveness of VNPs versus NRT will also be evaluated. Discussion: Further data are required to strengthen certainty of evidence for VNPs aiding smoking cessation, particularly for newer generation pod devices. To our knowledge, this trial is the first to offer choice of VNPs and no comparative effectiveness trial data exists for new pod devices. If effective, the findings can inform wider implementation of VNPs to aid smoking cessation in a priority group. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12621000076875. Registered on 29 January 2021. https://www.anzctr.org.a

“I’m not strong enough; I’m not good enough. I can’t do this, I’m failing”: a qualitative study of low-socioeconomic status smokers’ experiences with accessing cessation support and the role for alternative technology-based support

Abstract Background The social gradient in smoking rates persist with an overrepresentation of smoking and its associated harms concentrated within lower socioeconomic status (SES) populations. Low-SES smokers are motivated to quit but face multiple barriers when engaging a quit attempt. An understanding of the current treatment service model from the perspectives of treatment-seeking low-SES smokers is needed to inform the design of alternative smoking cessation support services tailored to the needs of low-SES populations. This qualitative study aimed to: i) explore low-SES smokers’ recent quitting experiences; ii) assess factors that impact treatment engagement; and iii) determine the acceptability and feasibility of alternative approaches to smoking cessation. Method Low-SES participants (n = 24) previously enrolled in a smoking cessation RCT participated in either a semi-structured focus group or in-depth telephone interview. Data was obtained and analysed using thematic analysis from October 2015 to June 2016. Analysis was deductive from the interview guide and supplemented inductively. Results Participants expressed feelings of guilt and shame around their smoking behaviour and experienced stigmatisation for their smoking. Guilt, shame, and stigmatisation negatively impacted treatment seeking behaviours with most avoiding current quit services. Costs of pharmacotherapy and treatment adherence were commonly cited barriers to treatment success. Electronic-cigarettes were perceived to be unsafe due to uncertainty on their legal status and regulatory restrictions. Technology-based text-messaging quit support was endorsed as a more favourable alternative compared to existing behavioural treatment services. Conclusion Stigmatisation was commonly endorsed and acted as an impediment to current treatment utilisation. Electronic-cigarettes may present a viable harm reduction alternative, but their likely uptake in socioeconomically disadvantaged groups in Australia is limited by smokers’ uncertainty about their regulation and legality. Mobile phone based cessation support may provide an alternative to telephone counselling and overcome the stigmatisation low-SES smokers face while trying to quit

Changes in mental health and help-seeking among young Australian adults during the COVID-19 pandemic: a prospective cohort study.

BACKGROUND: Young people may have elevated risk for poorer mental health during the coronavirus disease 2019 (COVID-19) pandemic, yet longitudinal studies documenting this impact are lacking. This study assessed changes in mental health and help-seeking since COVID-19 restrictions in young Australians, including gender differences. METHODS: Data were drawn from a recent subsample (n = 443; 60% female; Mage = 22.0) of a prospective cohort originally recruited in secondary school to complete annual surveys. The subsample completed an additional COVID-19 survey during COVID-19 restrictions (May-June 2020), which was compared to responses from their latest annual survey (August 2019-March 2020). Mixed effect models with time and gender as the primary predictors were conducted for: (i) scores on the Patient Health Questionnaire Depression 9-item (PHQ-9) and Generalised Anxiety Disorder 7-item (GAD-7) modules assessed before and during COVID-19 restrictions, and (ii) self-reported help-seeking from a health professional in February 2020, and the month preceding May-June 2020. RESULTS: Mean symptom scores increased from before to during COVID-19 restrictions on the PHQ-9 (coefficient: 1.29; 95% CI 0.72-1.86) and GAD-7 (0.78; 95% CI 0.26-1.31), but there was no increase in help-seeking over time (odds ratio 0.50; 95% CI 0.19-1.32). There was no evidence of differential changes by gender. CONCLUSIONS: This study found increases in depression and anxiety symptoms but not greater help-seeking among young Australian adults during the first wave of the pandemic. Increasing availability and awareness of accessible treatment options and psychoeducation is critical, as well as further research into risk and protective factors to help target treatment to this vulnerable age group

The experience of physiological and psychosocial alcohol-related harms across adolescence and its association with alcohol use disorder in early adulthood : A prospective cohort study

BACKGROUND: Different forms of alcohol-related harm (e.g., hangovers, fighting) may confer differential risk of clinically relevant alcohol problems. We examine: (i) patterns of transition in experiencing alcohol-related harms across adolescence; (ii) whether factors in early adolescence predict transition patterns; and (iii) whether transition patterns predict later alcohol use disorder (AUD) symptoms. METHODS: We used a longitudinal Australian cohort (n = 1828) to model latent class transition patterns of alcohol-related harms across three timepoints (Mage = 13.9, 16.8, 18.8 years). Regression models assessed whether child, peer, and parent factors in early adolescence (Mage = 12.9) predicted harms transition patterns and whether these patterns predicted AUD symptoms in early adulthood (Mage = 19.8). RESULTS: Five transition patterns characterized most of the cohort (n ≈ 1609, 88.0%): (i) minimal harms (n ≈ 381, 20.8%); (ii) late physiological harms (n ≈ 702, 38.4%); (iii) early physiological harms (n ≈ 226, 12.4%); (iv) late all harms (n ≈ 131, 7.2%); and (v) gradual all harms (n ≈ 169, 9.2%). With late physiological harms as the reference, females had increased risk of experiencing early physiological harms (relative risk [RR]: 2.15; 99.5% CI: 1.19, 3.90). Late all harms (RR: 1.71; CI: 1.19, 2.47) and gradual all harms (RR: 1.84; CI: 1.37, 2.47) were each associated with increased odds of meeting criteria for AUD, even when patterns of alcohol consumption are considered. CONCLUSIONS: Adolescents display heterogeneous transition patterns across physiological and psychosocial alcohol-related harms. Females are at greater risk of experiencing early physiological harms. Experience of both physiological and psychosocial harms in late adolescence is an important and potentially modifiable precursor to clinically relevant alcohol problems in early adulthood

Parental supply of sips and whole drinks of alcohol to adolescents and associations with binge drinking and alcohol-related harms: A prospective cohort study

Background: Parents frequently supply alcohol to their children, often only sips. We investigated whether supply of sips and whole drinks, from parents and other sources, are differentially associated with subsequent drinking outcomes. Methods: A cohort of 1910 adolescents (mean age 12.9yrs) were surveyed annually over seven years from 2010−11. We examined prospective, adjusted associations between the quantity of supply from parental and non-parental sources in the preceding 12 months and five outcomes in the subsequent year, over several consecutive years: binge drinking; alcohol-related harms; symptoms of alcohol abuse, dependence and alcohol use disorder (AUD). Results: In early waves, most parental supply comprised sips, while supply of whole drinks increased in later waves. Among those not receiving alcohol from other sources, parental supply of sips was associated with increased odds of binge drinking (OR: 1.85; 99.5 % CI: 1.17–2.91) and alcohol-related harms (OR: 1.70; 99.5 % CI: 1.20–2.42), but not with reporting symptoms of alcohol abuse, dependence or AUD, compared with no supply. Relative to no supply, supply of sips from other sources was associated with increased odds of binge drinking (OR: 2.04; 99.5 % CI: 1.14–3.67) only. Compared with supply of sips, supply of whole drinks by parents or others had higher odds of binge drinking, alcohol-related harms, symptoms of dependence and of AUD. Secondary analysis demonstrated that supply of larger quantities was associated with an increased risk of all outcomes. Conclusion: Parental provision of sips is associated with increased risks and the supply of greater quantities was associated with an increasing risk of adverse outcomes. Clinical Trial Registration: ClinicalTrials.gov (NCT02280551)

Effect of Cytisine vs Varenicline on Smoking Cessation: A Randomized Clinical Trial

IMPORTANCE: Cytisine is more effective than placebo and nicotine replacement therapy forsmoking cessation. However, cytisine has not been tested against the most effective smokingcessation medication, varenicline, which is associated with adverse events known to lead todiscontinuation of therapy.OBJECTIVE: To examine whether standard cytisine treatment (25 days) was at least aseffective as standard varenicline treatment (84 days) for smoking cessation.DESIGN, SETTING, AND PARTICIPANTS: This noninferiority, open-label randomized clinical trialwith allocation concealment and blinded outcome assessment was undertaken in Australiafrom November 2017 through May 2019; follow-up was completed in January 2020. A totalof 1452 Australian adult daily smokers willing to make a quit attempt were included. Datacollection was conducted primarily by computer-assisted telephone interview, but there wasan in-person visit to validate the primary outcome.INTERVENTIONS: Treatments were provided in accordance with the manufacturers’recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially thengradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standardtelephone behavioral support.MAIN OUTCOMES AND MEASURES: The primary outcome was 6-month continuous abstinenceverified using a carbon monoxide breath test at 7-month follow-up. The noninferiority marginwas set at 5% and the 1-sided significance threshold was set at .025.RESULTS: Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years;742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuousabstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (riskdifference, −1.62% [1-sided 97.5% CI, −5.02% to ]; P = .03 for noninferiority). Self-reportedadverse events occurred less frequently in the cytisine group (997 events among 482participants) compared with the varenicline group (1206 events among 510 participants) andthe incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002).CONCLUSIONS AND RELEVANCE: Among daily smokers willing to quit, cytisine treatment for 25days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiorityregarding smoking cessation

Effect of cytisine vs varenicline on smoking cessation: A randomized clinical trial

Importance: Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy. Objective: To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation. Design, Setting, and Participants: This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome. Interventions: Treatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support. Main Outcomes and Measures: The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at.025. Results: Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI, -5.02% to 8]; P =.03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P =.002). Conclusions and Relevance: Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation. Trial Registration: anzctr.org.au Identifier: ACTRN12616001654448