Title: What is the effectiveness of varenicline compared with nicotine replacement therapy for long term smoking cessation and clinically important outcomes such as mortality, myocardial infarction and frequency of service use? Evidence from the Clinical Practice Research Datalink
Funder: Department of Health and Social Care

Abstract: Rationale: Although varenicline has been shown to be effective for smoking cessation in randomised controlled trials, there have been few studies of its longer term (>1 year) effectiveness in real world settings or its effects on important clinical outcomes. In this project we will investigate the effects of varenicline compared to nicotine replacement therapies on long-term smoking cessation, and clinically-important outcomes such as rate of attendance to primary and secondary care, all-cause and cause-specific mortality, diagnosis of respiratory illness, myocardial infarction or depression and anxiety using a cohort of patients prescribed these medications from the Clinical Practice Research Datalink (CPRD). In a related Methodological Bolt-on funded by the Medical Research Council we will provide further validation of the instrumental variable methods we will use during the study: physicians’ prescribing preferences. This methodological bolt-on is broadly applicable to studies of the effects of pharmacotherapies using routine electronic medical records. Objective: To compare the effectiveness of varenicline with nicotine replacement products for long term smoking cessation and the impact of these treatments on health outcomes. Design: Observational cohort study using the CPRD, Cox-regression, propensity score matching and instrumental variable analysis using physicians’ prescribing preferences. Setting: Representative clinical population in the United Kingdom. Participants: Approximately 180,000 individuals from the CPRD who have been prescribed varenicline or nicotine replacement products since 2006. Intervention: Prescriptions of varenicline or nicotine replacement products. Outcomes: Smoking cessation up to nine years post prescription derived from smoking indicators in the CPRD. Health outcomes including: frequency of attendance of primary care, frequency of hospitalisation, all-cause and cause-specific mortality, diagnosis of respiratory illness including Chronic Obstructive Pulmonary Disease (COPD), diagnosis of myocardial infarction or diagnosis of depression or anxiety.

Lay abstract: In this study we will provide important new information about the effects of the smoking cessation medication varenicline. We know from randomised trials that smokers who take a course of this drug are much more likely to successfully quit smoking in the short term. However, some recent research has suggested that patients prescribed varenicline might be more likely to have psychiatric problems or heart attacks. The evidence from randomised trials is not necessarily informative about the effects of varenicline when used in everyday clinical settings. For example, patients prescribed varenicline by GPs as part of their day-to-day care may be very different from participants recruited to a pharmaceutical trial. To address this gap in the evidence, in this study we will use data from the Clinical Practice Research Datalink, which contains information from electronic medical records of patients attending GP practices across the UK. We will investigate if patients prescribed varenicline are more likely to successfully abstain from smoking in the long term. We will also investigate whether by prescribing varenicline, and helping their patients quit smoking, GPs can help reduce the frequency that their patients attend the GP and are admitted to hospital. This is an important outcome because smoking related illnesses are a significant burden on the NHS’s resources. We will also investigate if prescribing varenicline affects whether patients develop significant side-effects such as respiratory illnesses, heart attacks or depression. Finally, one of the novel features of our study is that we will employ a number of different statistical approaches to check whether our results are reliable evidence that varenicline actually causes these outcomes. This is an important issue when using non-experimental data, and our previous studies have suggested that recently developed statistical techniques may help. In a Methodological Bolt-On attached to this project, which is funded by the Medical Research Council, we will provide further evidence and guidance about when these statistical techniques may be helpful for regulators, clinicians and patients.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH