HARMONY (HARM reduction for Opiates, Nicotine and You): Statistical Analysis Plan for a Randomised Controlled Trial of the Effectiveness of Vaporised Nicotine Products for Tobacco Smoking Cessation amongst NSW Opiate Agonist Treatment Clients

ABSTRACT Background The HARMONY study is a multicentre, randomised, single-blinded parallel group trial. It will compare the effectiveness of a 12-week course of liquid nicotine delivered via vapourised nicotine products (VNPs) to best practice nicotine replacement therapy (NRT) for smoking cessation in individuals receiving opiate agonist treatment (OAT). The aim of publishing this statistical analysis plan is to make the pre-specified statistical principles and procedures to be performed in the analysis of data generated by the HARMONY study, publicly accessible prior to the commencement of data analysis. Methods The plan outlines the analysis procedures for analysing the primary outcome of self-reported 7-day point prevalence abstinence from tobacco after 12-weeks of treatment. Secondary outcomes include biochemically verified abstinence, self-reported 30-day abstinence, number of cigarettes smoked each day, craving and withdrawal symptoms, and VNP safety. Between-group comparisons will be conducted at end of treatment, and at 12-weeks post-treatment. Researchers collecting outcome data are blind to the treatment group of each participant. Analysis Bayesian hierarchical models will be used to estimate the treatment effects for all outcomes with uninformative prior distributions for all effect parameters. Alongside the treatment effect estimate of each outcome, a 95% credible interval (highest posterior density), Bayes factor, and probability of direction will be presented. The analyses will be performed under an ITT framework assuming missing at random. All missing outcome and baseline data will be multiply imputed with predictive mean matching. Conclusion Making the statistical analysis plan for the HARMONY study publicly accessible prior to the commencement of data analysis minimises the risk of bias in the analysis of data, and the interpretation and reporting of results generated by the study. Registration The study was registered in the Australian New Zealand Clinical Trials Registry (Reference ACTRN12621000148875).