Smokers who were interested in the study were provided with the patient information sheet. If they decided to take part, they were invited to the baseline visit, arranged where possible to coincide with their hospital appointments.
Baseline visit and informed consent procedures
At the baseline visit, a research midwife further explained the study and any queries were discussed. Eligibility to take part in the study was then checked, and participants signed the informed consent form and were given a copy for their records. Midwives taking consent undertook Good Clinical Practice training. After providing consent, participants were asked to complete a baseline questionnaire and to provide a saliva sample (which was then posted to HAL). They were then randomised to use either NPs or ECs. The midwife then demonstrated the relevant product to the participant and answered any questions. A convenient date and time was then arranged for the first support call with the stop-smoking advisor. This was usually in a week’s time.
Participants were informed that their product would be posted to them in time for their first call (for details see Interventions).
To limit contamination, participants were asked, should they wish to use the non-allocated product (ECs in the NP arm and NRT in the EC arm – use of other NRT products than patches in the NP arm was allowed), to refrain from doing so for at least the first 4 weeks of the intervention period.
Eligibility confirmation
Medically qualified site Principal Investigators (PIs) (usually a senior obstetrician) were asked to review the study documents and confirm the participants’ eligibility. As the site PIs were not present at baseline visits, this was normally done following randomisation, but PIs were blinded to treatment allocation during this process. In eight cases (four in each study arm), randomised participants were withdrawn before starting the intervention. In four cases the PIs considered the participants ineligible, in one case only verbal consent was taken, one pregnancy was terminated before the study product was received and one participant was using patches daily. One participant was randomised twice.
Interventions
E-cigarette arm
Participants were provided with a Tobacco Product Directive approved refillable EC starter kit (One Kit by the UK ECIG STORE®, Wembley, UK), together with two 10 ml bottles of tobacco-flavoured e-liquid (18 mg/ml) and a pack of five replacement coils. An instructional leaflet was also provided (see Appendix 2). The EC starter pack was posted to participants a few days ahead of their first support call. Further supplies of e-liquid were posted out to participants for up to 8 weeks. A lower strength e-liquid (11 mg) and fruit flavours were available if participants did not like the original e-liquid posted out, and participants were encouraged to shop around if these were also unsuitable or they preferred a different EC device to the one provided.
Nicotine patch arm
Participants were posted an initial 2-week supply of Nicorette® Invisi (McNeil Products Ltd., High Wycombe, UK) 15 mg/16-hour NPs a few days ahead of their first support call. They were instructed to use them every day, placing them on a suitable area of the skin in the morning upon waking and removing before bedtime. Further supplies were posted out to participants for up to 8 weeks. A lower strength patch (10 mg/16 hours) was available as an alternative. Participants were encouraged to seek out other NRT products (such as the gum, lozenges, spray, etc.) via their general practitioner (GP) or local SSS if they felt they were struggling with the patch alone. Standard stop-smoking advice was also provided (see Weekly support calls).
Weekly support calls
Participants in both arms were scheduled to receive six support calls on a weekly basis. The support provided followed that of usual advice given in the UK SSS35 and was conducted by trained stop-smoking advisors. Calls were scheduled at times convenient to the participants. If calls were not answered, a further two attempts to contact the participant were made via phone, followed by a text asking for when would be a good time to call.
A text reminder was sent the day before the first call. At this first call, the receipt of the product was checked and participants were guided on how to use it. They discussed their past experience with quit attempts and set up their target quit date (TQD). Participants could choose to start using their product immediately or wait until the TQD.
A second call was conducted on or near the TQD. The advisor checked on any product issues and discussed quitting strategies (e.g. preparing for the TQD, avoiding triggers to smoking and distracting themselves with other tasks). Participants were encouraged to avoid taking even a single puff of a cigarette from the TQD onwards and to use their products on a regular basis. The first call took up to 20 minutes, the other calls took on average 10 minutes.
If participants wanted to have their TQD straight after the first call, the contents of the first and second calls were combined.
During the further four weekly calls, the advisors checked on clients’ progress, supplies of e-liquid/patches and any product-related issues, and offered guidance on maintaining abstinence/stopping smoking. At the final call, participants were given information on how to get further product supplies if they wished to continue using the products (e.g. purchase own e-liquid or obtain NRT prescriptions from GP or from local SSS) and were informed that a final supply could be sent out to them in the next 2 weeks upon request. Participants were also reminded that they would be contacted for a follow-up around their due date.
Follow-up calls
Two follow-ups were conducted, one at the EOP to collect effectiveness and safety data and another at 3 months post partum, requested by the study funder, to collect additional health outcomes of the mother and infant. Text reminders were sent prior to these calls. If participants were not contactable via phone, then emails, texts, postal and online questionnaires were sent to obtain the data. The follow-up efforts at EOP used the following protocol: two calls and text in week 1; two calls and text in week 2; one call in week 3 followed by posting a questionnaire, emailing it and a text; no contact during weeks 4–5 to allow return of questionnaires; two calls in week 6; one text in week 7; two calls in week 8; one text in week 9; one call in week 10; one text in week 11 followed by an email; one call in week 12; one text in week 13; one call in week 14; and a final text in week 15. The follow-up efforts at 3 months post partum were as follows: two calls and text in week 1; one call in week 2 followed by posting and emailing of questionnaire and a text; no contact during weeks 3–4 to allow return of questionnaires; one call and one text in week 5; and a final call in week 6.
To prevent distress to participants, the co-ordinating office sent a list of participants due for follow-up to the local research teams to identify participants who had experienced an event which could make follow-up distressing, and to advise whether follow-up should be attempted. A text reminder was also sent to all participants the day before their follow-up call was due to take place. Participants were asked to text back if they did not wish to be called. Participants were also able to text back their smoking status if a call was not convenient.
As the majority of pregnant smokers who abstain during pregnancy return to smoking after delivery,6,36 the first follow-up call was made at 35 weeks’ gestation. Following an example from a recent trial,37 to increase the chance of reaching participants, the period for data collection was from 35 weeks’ gestation to 10 weeks post estimated delivery date.
Participants reporting abstinence from smoking, those who were using both cigarettes and NRT/ECs (‘dual users’) and those who reported a reduction of cigarette consumption of 50% or more were asked to provide a saliva sample. Saliva sample kits and instruction on use were posted with a self-addressed envelope for the return of the sample. Once received by the study team, the participants were sent a text to thank them and £20 was sent in the post for their time and effort.
During the last 14 months of the study, we also asked self-reported abstainers using nicotine-containing products to attend local study sites to provide a CO reading. Once the site sent the CO reading to the study team, the participants were sent a text to thank them and £20 was sent in the post for their time and effort.
A further amendment was approved in January 2020 to see if any improvement in sample returns could be achieved by including £10 with the sampling kit (an upfront payment) and sending a further £10 when the saliva sample was returned (total remained £20). This was implemented in February 2020.
