Caldwell 2014.

Study characteristics
Methods	Study design: parallel RCT Country: New Zealand Recruitment: from media advertisements, clinician referrals, and a database of people interested in trying to stop smoking
Participants	1423 smokers: aged 18 to 70 years, ≥ 9 cigarettes per day, FTND ≥ 3. Ineligible if currently taking psychoactive medication/illicit drugs, drank > 28 units of alcohol a week, had hyperthyroidism/diabetes/severe renal or hepatic disease, were female and using inadequate contraception or were breastfeeding 46% men; mean age 45; average cigarettes per day: 20; mean FTND: 6.1
Interventions	1) 6 months of nicotine oral spray parallel to 5 months of free 24‐hour nicotine patch. Each spray actuation contained 1 mg nicotine. 2. 6 months of placebo oral spray parallel to 5 months of free 24‐hour nicotine patch. The placebo spray was dispensed in opaque bottles identical to the nicotine spray. Both groups were instructed to use the spray ad libitum whenever they felt the urge to smoke, up to a maximum of 30 sprays/day. Both groups received 21 mg/24‐hour nicotine patches for 18 weeks, then 14 mg/24‐hour nicotine patches for 2 weeks, and then 7 mg/24‐hour nicotine patches for 2 weeks.
Outcomes	Prolonged abstinence at 12 months' post‐quit day; CO‐validated (< 10 ppm). Prolonged abstinence defined as no smoking since end of grace period (4 weeks after quit day) to 12 months' post‐quit day Other abstinence measures: 7‐day PPA at 12‐month follow‐up (CO‐validated) Adverse events: measured for 12 months (treatment was for 6 months)
Notes	Authors provided information on dosing schedule Funding for the study was provided by the Health Research Council of New Zealand (HRC 09/200). Active Zonnic mouth‐spray was provided by Niconovum. Placebo Zonnic was manufactured by Argenta according to instructions from Niconovum. Nicotine patches were provided without charge by the New Zealand Ministry of Health. Conflicts of interest: none
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation sequence was computer‐generated. Quote: "Subjects were randomised centrally for all three trial sites using a random allocation algorithm built into the access database that was used for all of the data collection"
Allocation concealment (selection bias)	Low risk	Study participants were allocated into groups by a computer.
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blinding maintained throughout trial Quote: "Active and placebo bottles were identical", "all staff remained blind to the allocation during the course of the trial"
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropout rates at 12 months were 612/716 for group 1 (nicotine spray plus nicotine patch), and 621/707 for group 2 (placebo spray plus nicotine patch). There was more than 50% dropout overall, but rates were similar between groups.