title: What are the effects of varenicline compared with nicotine replacement therapy on long-term smoking cessation and clinically important outcomes? Protocol for a prospective cohort study.
abstract: BACKGROUND
  Smoking is a major avoidable cause of ill-health and premature death. Treatments that help patients successfully quit smoking have an important effect on health and life expectancy. Varenicline is a medication that can help smokers successfully quit smoking. However, there are concerns that it may cause adverse effects, such as increase in the occurrence of depression, self-harm and suicide and cardiovascular disease. In this study we aim to examine the effects of varenicline versus other smoking cessation pharmacotherapies on smoking cessation, health service use, all-cause and cause-specific mortality and physical and mental health conditions.
  
  
  METHODS
  In this project we will investigate the effects of varenicline compared to nicotine replacement therapies on: (1) long-term smoking cessation and whether these effects differ by area level deprivation; and (2) the following clinically-important outcomes: rate of general practice and hospital attendance; all-cause mortality and death due to diseases of the respiratory system and cardiovascular disease; and a primary care diagnosis of respiratory illness, myocardial infarction or depression and anxiety. The study is based on a cohort of patients prescribed these smoking cessation medications from the Clinical Practice Research Datalink (CPRD). We will use three methods to overcome confounding: multivariable adjusted Cox regression, propensity score matched Cox regression, and instrumental variable regression. The total expected sample size for analysis will be at least 180,000. Follow-up will end with the earliest of either an 'event' or censoring due to the end of registration or death.
  
  
  BACKGROUND
  Ethics approval was not required for this study. This project has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will disseminate our findings via publications in international peer-reviewed journals and presentations at international conferences.
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Davies
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Taylor
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK School of Experimental Psychology, University of Bristol, Bristol, UK.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Taylor
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Kyla H
authors.initials: KH
authors.lastname: Thomas
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK Department of Economics, University of Bristol, Bristol, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Windmeijer
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK School of Experimental Psychology, University of Bristol, Bristol, UK.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Munafò
mesh_terms: D001007:Anxiety; D003863:Depression; D006801:Humans; D016015:Logistic Models; D015999:Multivariate Analysis; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D012907:Smoking / Q000188:drug therapy* / Q000453:epidemiology; D016540:Smoking Cessation / Q000379:methods* / Q000523:psychology*; D012959:Socioeconomic Factors; D013405:Suicide; D061485:Tobacco Use Cessation Devices / Q000009:adverse effects; D000068580:Varenicline / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D018722:Nicotinic Agonists; D000068580:Varenicline
keywords: EPIDEMIOLOGY; INTERNAL MEDICINE; STATISTICS & RESEARCH METHODS