Hajek 2022.

Study characteristics
Methods	Design: RCT multicentre Participants: Pregnant smokers (12 to 24 weeks gestation) who smoke daily and are interested in stopping smoking Setting: Maternity services across the UK. 23 hospital sites across England and one National Health Service Stop Smoking Service in Scotland Recruitment: Recruitment was managed by research midwives in England and by the Stop Smoking Service in Scotland. Participants were identified from patient records and sent study information and invitation letters or invited via telephone, email or text; approached in person when attending antenatal hospital appointments; referred by community midwives or stop‐smoking advisors; or self‐referred via posters advertising the study at the sites’ antenatal clinics. Study start date: 01/05/2017. Study end date: 26/11/2020
Participants	Total N: 1140 EC arm: 571 NRT arm: (nicotine patches) 569 Inclusion criteria: 12 to 24 weeks pregnant, daily smoker, wants help with stopping smoking. Willing to be randomised to use either NRT or EC and agreeing to use only the allocated stop‐smoking product for at least the first 4 weeks of their quit attempt. Exclusion criteria: Allergy to nicotine skin patches. Current daily use of NRT or e‐cigarettes, and serious medical problems or high‐risk pregnancy Inclusion based on specific population characteristic: Pregnant women Female 100%. Mean age 27. Mean CPD 10  E‐cigarette use at baseline: No Motivated to quit: Yes
Interventions	EC: Refillable Arm 1: EC Participants were sent an EU Tobacco Product Directive‐compliant refillable e‐cigarette starter kit (One Kit by the UK E‐cig Store), together with two 10 mL bottles of tobacco‐flavoured e‐cigarette liquid (1.8% nicotine; 70% propylene glycol and 30% vegetable glycerol), a pack of five replacement coils, and an instruction leaflet (Supplementary Data, Appendix 5). Further supplies of e‐cigarette liquid were posted on request for up to 8 weeks. A lower strength e‐cigarette liquid (1.1%) and e‐cigarette liquid with fruit flavour were available as alternatives. Participants were encouraged to source e‐cigarette liquids of the strength and flavour they liked, as well as different e‐cigarette devices, and arrange their own supplies after 8 weeks if needed. The cost of the kit provided by the study was £22.75 and the cost of e‐cigarette liquid was up to £24 for an 8‐week supply. Products used during the initial 4 weeks (n = 344) # * N (%): Refillable e‐cigarettes 324 (94.2%); Cig‐a‐like 1 (0.3%); Cartridge/Pod 1 (0.3%); Information missing 18 (5.2%). Nicotine strength N (%): 0 mg/mL 7 (2.0); 1‐10 mg/mL 47 (13.7); 11‐20 mg/mL 199 (57.9); Information missing 91 (26.5)   Arm 2: NRT ‐ Nicotine patches Participants were sent an initial 2‐week supply of Nicorette Invisi 15 mg 16 h nicotine patches with manufacturer instruction leaflets and instructed to apply patches every day upon waking, and remove them before bedtime. Further supplies were posted on request for up to 8 weeks. A lower strength patch (10 mg 16 h) was available as an alternative. Participants were encouraged to access further supplies themselves via their general practitioner or local Stop Smoking Service. This could be patches and/or other NRT products such as nicotine chewing gum, inhalator or mouth spray, to use in addition to the patch alone if needed. In the United Kingdom, pregnant women who smoke receive NRT free of charge. Behavioural support was given that accompanied both study arms. Participants received six phone calls from stop‐smoking advisors who followed the practice of the UK Stop Smoking Service 61.
Outcomes	Baseline, weeks 1‐4 after target quit date (TQD) (phone call), end of pregnancy (EOP) at least 6 months (saliva & CO), 3 mths post‐partum (phone call) Cessation: saliva samples & carbon monoxide readings collected AEs & SAEs Continued use of study product Flavours EC nicotine strength
Study funding	The study was funded by the National Institute of Health Research, Health Technology Programme (ref. no. 15/57/85). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. For part of the trial F.P. was supported by Cancer Research UK (grant no. C8162/A25356).
Author declarations	P.H. provided consultancy to and received research funding from Pfizer. D.P. received research funding from Pfizer. H.M. has received honoraria for speaking at smoking cessation educational events and sitting on an advisory board organized by Pfizer. All other authors have no competing interests.
Notes	New to 2022 update
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "An independent statistician developed the randomization sequence using permuted block randomization with a block size of at least 6 and a maximum of 12".
Allocation concealment (selection bias)	Low risk	Quote: "The randomization list was accessible only to the independent statistician, on a secure server. Researchers conducting randomization used the database application to inform the participants of their study arm allocation. Researchers conducting follow‐up calls were blind to treatment allocation until the follow‐up contact was made".
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants received equally intensive interventions.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Researchers conducting follow‐up calls were blind to treatment allocation until the follow‐up contact was made. Once contact was made and the trial application was opened, condition‐specific questions were visible on the computer screen. The trial statistician was blind to participant allocation until the analysis of the primary and secondary outcomes was complete. This was achieved by extracting and importing into Stata only the baseline characteristics, study arm and smoking status variables in the first stage of the analysis. Variables coding treatment adherence and product use were extracted only after the primary and secondary outcome analyses were completed".
Incomplete outcome data (attrition bias) All outcomes	Low risk	EC arm 515/571. NRT arm 495/569
Selective reporting (reporting bias)	Low risk	Analysis prespecified