Begh 2021.

Study characteristics
Methods	Individually randomized, blinded, 2‐arm trial Setting: 39 general practices, England Recruitment: Primary care registries
Participants	325 (164 intervention; 161 intervention) 47.4% female. Mean age 57.8. Mean cpd 20.1. Mean FTCD 4.2 Inclusion criteria: Current smoker ≥ 10 ppm for exhaled CO and smokes a minimum of 8 cigarettes/8 grams of tobacco per day (including pipe, cigars or tobacco roll‐ups) with no intention of stopping immediately or seeking cessation support. Diagnosed with 1 or more of the following chronic conditions: ischaemic heart disease, peripheral vascular disease, hypertension, diabetes mellitus (Type 1 and Type 2), stroke, asthma, COPD, chronic kidney disease, depression, schizophrenia, bipolar disorder or other psychoses. Informed consent. ≥ 18 years Exclusion criteria: GP believes that switching to EC would not benefit the patient, given their current medical condition; currently using EC, NRT or other cessation therapies (e.g. bupropion, nortriptyline or varenicline); plans to stop smoking before or at the annual review; currently enrolled in another smoking‐related study or other study where the aims of the studies are incompatible; cannot consent due to mental incapacity; pregnancy, breastfeeding
Interventions	EC type: refillable Control: No additional support beyond standard care. Intervention: practitioners gave brief advice about EC and offered participants a free EC for the purpose of switching from smoking to vaping. The instruction was to reduce their smoking. If the offer was accepted, participants received: a starter pack containing an Aspire PockeX all‐in‐one e‐cigarette, 2 x 0.6 ohm coils and 1 x 1.2 ohm coil, 3 nicotine e‐liquids in 18 mg/mL (blueberry, menthol) and 12 mg/mL (mixed fruit) strengths and an accompanying practical support booklet developed by the study team. The practical support booklet contained information on how to set up the device, correct ways to vape, common issues with use and a list of local vape shops. It included motivational support to reinforce practitioners’ advice about EC, including the benefits of cutting down on cigarettes through e‐cigarette use and addressing perceived risks and concerns. It included links to a study‐dedicated website with video demonstrations on how to use EC and testimonials. Participants could opt into receiving an introductory telephone call from an experienced vaper in the first week of receiving their EC, to guide them on technical aspects of EC use (not behavioural support). Thereafter, participants could contact the vaper by telephone for up to 2 months after receiving their kit. All: Practitioners offered routine smoking cessation support to all participants. Although this varied across practices, standard care typically involved brief advice about stopping smoking and assistance to do so either by referral to the NHS stop smoking services or offer of pharmacotherapy. If the participant declined standard care, they were randomized by the practitioner to either the intervention or control arm. In the control arm, participants received no further support beyond standard care
Outcomes	0 months, consultation visit, 2 months post‐consultation, 8 months post‐consultation "Patients attended four visits at their GP practice: a baseline visit, a therapeutic visit (‘annual review’) with their GP or nurse and two follow‐up visits two months and eight months post‐consultation." Primary outcomes: • 7‐day PPA from smoked tobacco at 2 months, defined as complete self‐reported abstinence from smoking – not even a puff – in the past 7 days, accompanied by a salivary anabasine concentration of < 1 ng/ml If there are technical issues with the analysis of saliva samples (e.g. if there is not enough saliva present in the sample for anabasine analysis), we will use exhaled CO as verification of abstinence (CO < 10 ppm) (Deviation from SAP: CO used due to imprecision of values for anabasine) • Reduction in cigarette consumption at 2 months, defined as at least a 50% reduction in self‐reported cigarettes per day on each of the last 7n days at 2 months compared with baseline consumption, accompanied by evidence of reduced smoke intake indicated by a CO measurement lower than baseline Secondary outcomes: • 7‐day PPA measured at 8 months, biochemically confirmed by an exhaled CO of < 10 ppm • 6‐month prolonged abstinence using the Russell standard criteria, defined as smoking < 5 cigarettes between 2‐ and 8‐month follow‐ups, confirmed by an anabasine concentration of < 1 ng/ml at 2 months and an exhaled CO concentration of < 1 ng/ml at 8 months if CO measurement unavailable)  • Mean change in salivary anabasine concentration and CO from baseline to 2 months.  • Percentage reduction in self‐reported cigarettes per day from baseline to 2 months; and from baseline to 8 months. SAEs & AEs reported. AEs: throat/mouth irritation; cough; headache; palpitations; nausea; dry mouth; dizziness; shortness of breath; stomach pain
Study funding	NIHR Postdoctoral Fellowship and NIHR School for Primary Care Research funded randomized controlled trial
Author declarations	All authors declare no competing interests
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Participants were randomised to intervention or control with a 1:1 allocation ratio. A randomisation list was generated by the trial statistician using the current version of Stata and validated by a second statistician within the Primary Care Clinical Trials Unit (PC‐CTU). The randomisation was stratified by practice and used varying block sizes to ensure allocation concealment."
Allocation concealment (selection bias)	Low risk	Quote: "The randomisation list was passed to someone independent of the trial who created the randomisation envelopes. The trial statisticians were blinded to the treatment allocation during analyses"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Due to the nature of the trial, GPs and practice nurses were aware of the participant’s treatment allocation to ensure that the correct intervention was given. Therefore, practitioners who delivered the intervention could not be blinded to treatment. While participants knew whether they had been offered support to cut down by using an e‐cigarette or not by their GP or nurse, the participant was not informed that the study investigated this specifically and therefore were in some respects blind to allocation. Groups not matched for face‐to‐face contact time
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: “7‐day point‐prevalence abstinence from smoked tobacco at two months, defined as complete self‐reported abstinence from smoking – not even a puff – in the past seven days, accompanied by a salivary anabasine concentration of <1ng/ml” or exhaled CO as verification of abstinence (CO <10 ppm)."
Incomplete outcome data (attrition bias) All outcomes	Low risk	At 8 months: Control 144/161; Intervention 148/164
Selective reporting (reporting bias)	Low risk	Used CO above anabasine, but reported both (Deviation from SAP: CO used due to imprecision of values for anabasine) All predefined outcomes listed in the published protocol and clinical trial register are reported