Clinical trial NCT03717051
Conditions: Smoking Cessation
Keywords: intervention nicotine replacement sample smoking cessation smoking hotspots
Sponsor: The University of Hong Kong
Start date: 2018-10-13; Completion date: 2020-07-31
Enrollment: 834 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Background More than 60% of the daily smokers in Hong Kong have never tried and have no intention to quit smoking. About 30.8% of daily smokers attempted to quit but failed. Nicotine replacement therapy (NRT) is a safe and effective pharmacotherapy to reduce withdrawal symptoms during early stage of tobacco abstinence and increase quit rate. However, the prevalence of using NRT in Hong Kong is lower than most of the developed countries. The proposed project aims to test if providing free NRT sampling to smokers can increase quit attempt, the use of smoking cessation (SC) services and abstinence.

Methods University undergraduate students will be trained, and will invite smokers at outdoor smoking hotspots to quit smoking and enroll into SC services. Eligible smokers will be randomized to experimental or control group according to a cluster randomization, using recruitment session as the randomization unit. The experimental group will be provided with 1-week free NRT sampling and medication counselling, whereas the control group will be provided medication counselling. Both groups are advised to enroll in the SC services. The primary outcome is the proportion of smokers who report quit attempts at 1 month follow-up

Discussions The findings will inform the feasibility and effectiveness of delivering free NRT sampling to increase quit attempt, the use of smoking cessation services and abstinence. It will yield more information on smokers' adherence to the NRT sampling, side effect and safety issue of the usage.

Detailed description:
Study design

The proposed project has 4 phases: (1) Training of SC ambassadors (SCAs) for the SC promotion; (2) SC promotion sessions to deliver the medication counselling and NRT sampling (experimental group), or the advice to use NRT only (control group); (3) Follow-up of the recruited smokers; (4) Evaluation of the effectiveness of training, promotions, and use of NRT sampling. To examine the effectiveness of NRT sampling for recruitment and quitting, a multi-site cluster RCT (allocation ratio 2:1) will be used. All promotion sessions will be randomly allocated to either the experimental or the control group. The experimental group will receive medication counselling and NRT samples, while the control group only receive the advice to use NRT. Both groups are advised to enroll in any smoking cessation service in Hong Kong. Because smokers who receive NRT sampling will be more likely to participate in the study, the experimental sessions will then recruit more smokers than the control sessions. Hence, the allocation ratio of participants is arbitrarily set at 2:1. To increase comparability between the two groups, the promotion sessions of one hotspot will be randomly allocated to either group. All recruitment and quitting outcomes in the smokers between the experimental and control group will be compared.

Subjects

Smokers with the following inclusion criteria will be invited to participate in our RCT: (1) Hong Kong residents, (2) aged 18 to 65 years, (3) have used any tobacco products in the past month, (4) able to read and speak Chinese, (5) have not used NRT for the past month, (6) no severe angina, serious cardiac arrhythmias and hypertension, (7) have not suffered acute myocardial event in the past 4 weeks, (8) neither pregnant nor breastfeeding, (9) not under medication and treatment due to mental illness. To confirm the smoking status, in those who use conventional cigarettes, smokers' exhaled carbon monoxide will be measured on-site. Nurses will measure the blood pressure if smoker is aged over 50 years old, obese by observation, or upon patient requests.

The inclusion criterion no. 3 was "smoke 10 cigarettes or more per day in the past week" and is amended to "have used any tobacco products in the past month". The initial intention of setting the inclusion criteria of at least 10 cigarettes per day (CPD) is to recruit smokers who have moderate to strong level of craving and a greater need for NRT. However, we also recognize that one of the objectives of the research is to promote the use of NRT for quit attempts with NRT sampling. In fact, smokers who smoke less than 10 CPD can also benefit from using NRT gums. Therefore, the change in the inclusion criteria does not deviate from our research aim. In contrast, with the removal of the criterion for CPD, we will be able to reach out to a larger group of smoking population and encourage more smokers to use NRT to quit smoking.

Procedures

In the experimental sessions, the SCAs will approach and distribute souvenirs (e.g. a pen) or leaflets to the smokers at outdoor smoking hotspots for 3-4 hours. The souvenirs and leaflets will have SC messages, quitline number and other SC services. If a smoker is willing to accept them and talk to the SCAs, the SCAs will advise the smoker to quit using the AWARD protocol. The AWARD protocol includes (1) Ask the smoking history, (2) Warn about the high risk (i.e., half of the smokers will die of smoking-related diseases), (3) Advise to quit, (4) Refer to the SC clinics of TWGHs and (5) Repeat the above advice (Do-it-again) \[4\]. Our previous studies have shown that the AWARD protocol is a feasible and appropriate tool used by non-healthcare professionals to promote smoking cessation \[4-6\]. If the smoker is interested in smoking cessation, the SCAs will introduce NRT to the smoker and conduct a preliminary assessment of his/her eligibility for enrolling in the "NRT sampling" programme. The SCAs will invite him/her to go to the smoking cessation truck nearby to receive counselling by an onsite nurse. If the smoker is not eligible, he/she can still enroll in the cessation service provided by the SC clinics. The intervention and assessment will mostly be taken place in a smoking cessation truck when the recruitment venues allow us to park the truck nearby, or at outdoor areas when a parking space for a truck is not available.

Intervention: NRT sampling and medication counselling

In the experimental sessions, an onsite nurse will assess whether each participant is fit for using NRT with further assessment on his/her current physical status, medication and blood pressure. If the participant is willing to use NRT to quit smoking and pass the nurse's assessment, he/she will be prescribed the NRT sample, regardless of whether they use NRT for smoking reduction and when the quit day is. The nurse will help the participant decide which type of NRT product (gum: 2mg, patch: 14mg or 21mg) that he/she can use and advise him/her on how to use the NRT based on his/her smoking habit and daily cigarette consumption. In addition, the nurse will deliver medication counselling which addresses five main components: (1) the benefits for using NRT in quitting, (2) withdrawal symptoms due to smoking cessation, (3) side effects of NRT, (4) instructions for using NRT, and (5) making appointments for TWGHs SC clinics. An instruction card for using NRT will be given. Afterwards, the participant will receive 1-week free NRT. Our research staff will send the NRT sample via mail within 2 days.

In the control sessions, all the above procedures for the experimental group will be applied, except that they will not receive an NRT sample and an instruction card about the use of NRT. Instead, they will be advised to obtain free NRT by enrolling in the SC clinics. Both groups will receive a one-page leaflet provided by the SC clinics, and encouraged to make service appointments with the SC clinics. The leaflet briefly introduced this RCT, the use of NRT and the service provided by the smoking cessation clinics.

When the participant has finished the above procedures, the research assistant or trained ambassadors (under supervision of the research staff) or the nurse will introduce the trial of evaluating the effect of NRT sample and the outreach service and screen the eligibility of participating in the trial. If the participant is eligible, the research assistant will seek his/her consent to participate in the trial, and complete a baseline questionnaire.

Some smokers are willing to participate in the RCT, but they have no time to receive all intervention or complete all recruitment procedures at the hotspots. In these cases, the SCAs will only briefly introduce the RCT, ask the participants to give written consent. A nurse will contact these participants to complete the baseline questionnaire and deliver the intervention (medication advice and NRT prescription) within the same day. If the participants are in the experimental group, after the telephone counselling by the nurse, our research staff will send the NRT sample via mail within 2 days.

Randomization

We will use cluster randomization based on promotion session as the cluster unit because the procedures of individual randomization are difficult in outdoor areas as found in our pilot RCT. The PI will randomly allocate the promotion sessions within a hotspot to the 2 groups by a list of group allocation which is based on a list of random numbers from Excel programme. Each hotspot will have 2 or more promotion sessions, and each session will last for about 3-4 hours. If a hotspot has 2 promotion sessions on 1 single day, the 2 sessions will be allocated into the same RCT group, and we will organize 2 more promotion sessions in this hotspot on another day.

Allocation concealment

All recruitment staff will know the group allocation before each promotion session, so no group concealment can be done.

Blinding

Participants, recruitment staff and nurses cannot and will not be blinded to the intervention. Assessors of the follow-up outcomes and the research analysts will not be involved in the recruitment and intervention delivery, and will be blinded to the group allocation (single blindness).

Baseline assessments

Baseline information includes socio-demographics, current use of conventional and new tobacco products, such as heat-not-burn tobacco products and electronic cigarettes, history of quit attempts, and intention to quit. Nicotine dependence will be assessed by the Fagerström Test for Nicotine Dependence.24 Participants will also be asked about their self-efficacy in quitting, based on the perceived importance, difficulty and confidence to quit smoking on a Likert scale from 0 to 10.

Follow-up

All the smokers who consent to the follow-up will be contacted via telephone or WhatsApp around one week by a nurse or a trained research staff after recruitment. The aim of this follow-up is (1) to enquire if there is any progress towards smoking cessation and (2) encourage the use of NRT for a quit attempt and/or enrollment in SC services as soon as possible. If participants show no interest to quit, the nurse/research staff will use the "5R" approach to re-motivate the quitting intention. The "5R" approach is being adopted by the local and international smoking cessation guideline including the discussion on why quitting is important (relevance), hazards of smoking (risk), benefits of quitting (rewards), difficulties (roadblocks) and repeated quit attempts (repetition). If participants report any contra-indication(s) to NRT, the nurse/research staff will discuss the reasons with them, and, if necessary, refer the participants to the physician in the smoking cessation clinic.

At 1-, 3- and 6-month follow-up, the quitting outcomes will be assessed by a trained interviewer through telephone who is blinded to the subject's group status. A small amount (HK$50=US$6.4) of cash voucher will be offered to those who completed a follow-up survey. At 6-month follow-up, participants who reported no smoking in past 7 days will be invited for a biochemical validation of the abstinence. Participants with exhaled carbon monoxide 4ppm or below and saliva cotinine level below 10ng/ml will be considered as validated abstinence. Participants of the biochemical validation, no matter the abstinence status is confirmed, will be offered a HK$50 (US$6.4) cash voucher for the travel compensation.

Sample size determination

As we predicted that the recruitment sessions of providing free NRT samples will recruit more smokers, participant ratio of the 2 trial groups is arbitrarily set at 2:1. At the time we designed this trial, our preliminary analysis of the aforementioned pilot RCT showed that the rate of quit attempt in the intervention and control group was 26% and 12% at 3-month follow-up, respectively. We arbitrarily reduced these rates to 20% and 8% for 1-month follow-up. To detect a significant difference with normal test and a power of 95% and 5% significance level, we need 485 subjects in the RCT (allocation ratio 2:1; 323 vs 162). Based on the method of Eldridge et al. (2006),29 conservatively assuming that we could recruit 8 participants per session on average and the intra-cluster correlation coefficient was 0.1, the design effect is estimated to be 1.7. Thus, the minimum sample size required for the trial is 825 (=1.7 X 485) participants and 104 sessions in total. With the similar calculation, the required sample size for detecting a significant difference in the proportion of using any smoking cessation service is 421.

Statistical analysis

An independent data analyst will perform the data check of missing, duplication and validity on the completed dataset before analysis is done. All data will be de-identified in the data analysis. To assess the effect of NRT sampling to the process outcomes, the number of smokers who accept the brief advice or consent the RCT in each recruitment session will be the outcome variables of Poisson regression model, with group allocation as the predictor, and total number of approached smokers in that promotion session as the offset variable. Considering the possibility of correlated outcomes of participants within the recruitment session, an analysis by generalized estimating equations model, assigning session as a random effect, will be used to summarize the intervention effect on the primary outcome. The analysis adopted a longitudinal approach with an exchangeable structure for the correlation matrix of the outcome. Other secondary outcomes will be analyzed with either generalized estimating equations models (binary outcomes; e.g. tobacco abstinence) or linear mixed model (continuous outcomes; e.g. perceived importance to quit smoking). Both intention-to-treat (treating participants as smokers without quit attempts and no use of cessation services if they are lost to follow-up) and per protocol analysis will be done. Subgroup analysis of comparing the primary and secondary outcomes between participants receiving the nurse-led intervention onsite and those receiving the intervention via telephone will be done.

Arms: arm 1: The intervention group will receive nicotine replacement therapy (NRT) sampling and medication counseling. The nurse will help the subject to decide which NRT product (patch or gum) he/she can use and advise how to use the NRT based on his/her smoking habit and amount of cigarette consumption. In addition, the nurse will deliver medication counselling which addresses five main components: (1) the benefits for using NRT in quitting, (2) withdrawal symptoms due to smoking cessation, (3) side effects of NRT, (4) instructions for using NRT, and (5) making appointments for TWGHs SC clinics. Afterwards, the participant will receive 1-week free NRT, an education card about NRT and a one-page leaflet provided by the SC clinics. arm 2: The control group subjects will receive medication counseling. They will be advised to obtain free NRT by enrolling in the smoking cessation services, but will not be given the sampling. The same one-page leaflet will be provided by the SC clinics.
Interventions: intervention 1: Nicotine replacement therapy (NRT) sampling intervention 2: Medication counseling
Intervention descriptions: intervention 1: 1-week free NRT samples (patch or gum) intervention 2: Medication counseling

Protocol documents:
Prot_SAP_000.pdf: 
NRT_protocol_v4 
Page | 1 
STUDY PROTOCOL 
Use of nicotine replacement therapy (NRT) sample and brief smoking cessation 
advice for recruiting smokers to smoking cessation services and motivating quit 
attempts 
 
 
 
 
 
 
 
 
 
 
 
NCT number: NCT03717051 
Document date: June 30th, 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


NRT_protocol_v4 
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Use of nicotine replacement therapy (NRT) sample and brief smoking cessation 
advice for recruiting smokers to smoking cessation services and motivating quit 
attempts 
STUDY PROTOCOL 
1. Project title 
Use of nicotine replacement therapy (NRT) sample and brief smoking cessation advice for 
recruiting smokers to smoking cessation services and motivating quit attempts 
2. Investigators 
Principal Investigator 
Dr. Derek Yee Tak CHEUNG, Research Assistant Professor, School of Nursing, The 
University of Hong Kong  
Co-investigator 
Ms. Ching Han Helen CHAN, Supervisor (Smoking Cessation Service), Tung Wah Group 
of Hospitals 
Dr. Kin Sang HO, Medical Officer, Tung Wah Group of Hospitals 
Dr. Man Ping WANG, Assistant Professor, School of Nursing, The University of Hong 
Kong 
Dr. William Ho Cheung LI, Associate Professor, School of Nursing, The University of 
Hong Kong 
Prof. Tai Hing LAM, Chair Professor, School of Public Health, The University of Hong 
Kong 
3. Study sites 
Outdoor smoking hotspots: Outdoor public areas where smokers cluster to smoke near 
rubbish bins with an ashtray 
4. Aims of the project 
This project aims to motivate smokers to use SC services and/or have quit attempts by NRT 
sampling and brief SC advice. The objectives are: 
1. Deliver brief SC advice to the smokers who smoke at outdoor smoking hotspots 


NRT_protocol_v4 
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2. Promote the use of NRT for quit attempts with NRT sampling. 
3. Evaluate the effectiveness of NRT sample on the use of any SC service, quit attempts 
and abstinence. 
5. Outcomes 
Phase 1: Training outcomes 
The knowledge, attitude, and practice of SC among the participants in the workshop will 
be evaluated through completing a survey before and immediate after, and 6 months after 
the training. 
Phase 2: Process outcomes of the promotion 
The primary process outcomes are the number and proportion of smokers that can be 
recruited for further follow-up, including those who will not participate in the RCT but 
agree to enroll in the SC clinics. We hypothesize that the promotion sessions providing 
NRT sampling will recruit more smokers, and greater proportion of recruited smokers 
among those who will be approached than those sessions without NRT sample. Other 
secondary process outcomes include (1) total number of smokers who can be approached 
in outdoor urban places; and (2) number of smokers who accept the brief SC advice. All 
these indicators will be documented by the SCAs in the promotion sessions.   
Phase 3: Quitting outcomes 
The evaluation aims to assess the effectiveness of NRT sampling on using the SC services 
and quit attempts, by comparing the outcomes between the experimental group and the 
control group. The two primary outcomes include (1) the proportion of smokers who enroll 
in any SC service in Hong Kong within 1 month of the recruitment; and (2) the proportion 
of smokers who report quit attempts at 1 month follow-up. Secondary outcomes include (1) 
the above outcomes at 3-month follow-up; (2) self-reported use of NRT in past month at 1- 
and 3-month follow-up; (3) self-reported tobacco abstinence in past 7 days and 4 weeks at 
3- and 6-month follow-up; (4) biochemically validated abstinence at 6-month follow-up; 
(5) perceived importance, difficulty and confidence to quit smoking (score 0-10); (6) 
progression towards smoking cessation as measured by Incremental Behavior Change 
toward Smoking cessation (IBC-S) [1]. All self-reported outcomes will be assessed either 


NRT_protocol_v4 
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by telephone or WhatsApp by allocation-blinded interviewers at 1, 3 and 6 months after the 
recruitment. Self-reported quitters (no use of tobacco products for 7 days) will be invited 
for examination of exhaled carbon monoxide with a Smokerlyzer, and to undertake a saliva 
cotinine test. Validated quitters were defined by exhaled CO < 4 ppm and salivary cotinine 
< 10 ng/ml, which have been confirmed as the cut-off in clinical trials to verify smoking 
abstinence [2,3]. A HK$50 shopping voucher will be given for each participation of follow-
up and biochemical validation. We have much experience for the above and have reported 
these in many papers [4-8]. 
6. Estimated duration and commencement date 
 
Proposed starting date:               1 July 2018 
 Proposed study completion date:       30 June 2020 
    Expected final report date:            30 June 2020 
7. Scientific/historical background 
Health needs of the local community 
Smoking causes cancers, coronary heart diseases and many more chronic diseases. Hong 
Kong still has more than 640 thousands daily smokers [9], and half of them will die of 
smoking-related diseases [10]. Although free smoking cessation (SC) services and 
occasional promotion activities are available, about 30.8% of daily cigarette smokers in 
Hong Kong have tried but failed to quit smoking, and 63% have never tried and did not 
want to quit [9]. The existing SC services have difficulties to attract smokers to come 
forward, but service providers lack resources and cost-effective methods to recruit smokers 
proactively. More specific interventions to enhance the utilization of SC service and quit 
attempts are needed. 
Very few healthcare professionals can deliver SC counselling or other interventions in the 
busy clinical settings [11-13]. To promote SC in the community, brief SC advice (AWARD, 
See Implementation plan/Procedure) and training of non-healthcare professionals for 
delivery of simple SC advice have been well developed by our team in Hong Kong [5, 7]. 
Yet, the recruitment for smokers is still difficult as we have shown that “hardcore” smokers 
– who are less motivated to quit and less likely to seek service – are increasing in Hong 
Kong [14]. Also, more immediate quitting assistance is needed for the recruited smokers in 


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the community-based SC promotion [6, 15], as any delay can result in default.  
Smokers are addicted to tobacco because tobacco delivers nicotine to the central nervous 
system, which leads to the desired psychological reactions and induces dependence. In the 
early phase of quitting, the lack of nicotine causes withdrawal symptoms such as headache, 
coughing, difficulty in concentration etc. By slowly delivering nicotine to cope with the 
dependence, nicotine replacement therapy (NRT) is a safe and effective pharmacotherapy 
to reduce withdrawal symptoms during early abstinence and smoking reduction, which 
increases the quit rate by 4-fold in the longer term [16]. A recent study has shown that NRT 
works better than many other behavioral interventions for smoking cessation [17]. 
Although NRT can be purchased over the counter without doctor’s prescription, or obtained 
freely from local SC clinics, only 9.8% of quit attempters had used medications for their 
quit attempts [9]. The corresponding proportion in Australia, Canada, the UK and the USA 
is at least 30% [18, 19]. In contrast, over 80% of Hong Kong quit attempters relied on self-
determination [9], which has a low success rate and easily leads to smoking relapse. The 
low prevalence of using NRT may be due to the higher absolute price of NRT per day 
(US$5.43 per day) [8] than, say, in the USA (US$2.41–3.62 per day) [20], and the low 
utilization of SC services which provide free NRT.  
Although some social marketing of SC has been done in Hong Kong, very few programmes 
promote the use of NRT. Existing SC services provide free NRT to smokers, but the 
smokers must first enroll in the SC services. That means majority of smokers, who do not 
know or use SC services, have low literacy of NRT use and its effectiveness.   
To sum up, the following health care needs regarding SC promotion in Hong Kong should 
be addressed: (1) Many current smokers still have no quitting intention (2) Many smokers 
are unable to quit smoking using self-determination, (3) The low success rate of quitting is 
attributed to the under-utilization of existing SC service and low use of effective 
medications such as NRT.  
Literature review on others’ strategies to address these needs 
Proactive approach of smokers at outdoor smoking hotspots is a new strategy initiated by 
our team to promote smoking cessation. Smoking hotspots are non-smoke-free urban places 
where many smokers gather to smoke around a rubbish bin with an ash tray to collect 
cigarette butts. We applied this approach by training university students to deliver brief SC 


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intervention to the smokers at these hotspots [15]. The brief intervention included brief 
advice, printed materials and introduction of the quitline (1833183). This pilot study 
showed that this approach was feasible and accepted by the smokers [15].  
To further show the efficacy and cost for this approach, we obtained funding from the 
Health Care and Promotion Fund to extend the promotion and evaluate more outcomes in 
2014-15 (Ref no. 06130205). This funded project showed that the promotion approached 
3096 smokers and recruited 210 smokers at a reasonable cost, particularly for youth 
smokers and those who wanted to quit [6]. About 10% of the recruited smokers from 
smoking hotspots reported abstinence at 6-month follow-up. Upon the invitation of the 
Health Research Symposium 2017, we presented a paper about this study on 16 June 2017. 
The findings of this study has been published in a renowned tobacco and public health 
journal (Nicotine and Tobacco Research)[6]. 
Further developments and improvements are needed to increase the impacts. First, the 
recruited smokers in the community were not further given more tailored and intensive 
interventions, and therefore some particularly heavy-smoking smokers would feel difficult 
to quit. We found that about 72% of the recruited smokers had intention to quit, who should 
be receptive for further intervention. Second, majority of the approached smokers did not 
consent to the follow-up by counsellors. These smokers, who were similar to the majority 
of smokers in the community, probably chose to quit without seeking assistance from 
healthcare professionals [7], or were hardcore smokers who were less likely to notice or 
use available SC services [14].   
These service gaps could be filled by (1) designing more effective ways to motivate quitting 
intention, (2) providing more immediate information and motivation of using NRT in their 
quit attempts, (3) enhancing smokers to try NRT first, (4) enhancing the continuing access 
of NRT through enrolling in the SC services or purchasing NRT over-the-counter. 
Scientific evidence supporting the strategies to address these needs proposed in this project 
Providing NRT sample and brief advice to the non-help-seeking smokers who are recruited 
at smoking hotspots is novel and warrants further exploration. Receiving free NRT 
immediately after recruitment can reduce the financial and time cost for trying this effective 
medicine. Previous randomized trials have confirmed that the delivery of NRT sample (less 
than 5-week dosage) increased quit attempts and prolonged abstinence [21-23]. The NRT 


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sample also increased smokers’ motivation and confidence to quit [21, 22]. The smokers in 
these trials were recruited in the community, and they were either unmotivated to quit, or 
not ready to receive intensive smoking cessation. No or only brief counselling sessions 
were included in these interventions. Therefore, delivering NRT sample immediately after 
giving SC advice to the smokers may increase the motivation to quit and use of quitting 
assistance. Also, the findings from the studies above are particularly applicable to our SC 
promotion in smoking hotspots which targets similar smokers in the community.  
The feasibility and effectiveness of providing NRT sample at smoking hotspots is novel 
and has been preliminarily evaluated by our team. We propose 1-week NRT as it is the 
cheapest and has been shown that the effectiveness on abstinence was similar to 2-week 
NRT [24]. In a feasibility study conducted by the SC clinics of Tung Wah Group of 
Hospitals (TWGHs), about three quarters of the approached smokers at outdoor smoking 
hotspots (77.6%, 548/706) accepted NRT sample. In the smokers who received the NRT 
sample, about 40.1% (n=220) enrolled in the SC service. In our recent pilot randomized 
controlled trial (RCT), we examined if 1-week NRT could improve quitting outcomes in 
the smokers who were recruited at smoking hotspots. The study protocol has been published 
in the journal Trials [25]. In all the invited smokers in the recruitment, the proportion of 
participation was very high (81.3%). The preliminary results showed that NRT sampling 
substantially increased use of NRT (34% versus 2%, Risk ratio = 17.00, 95% CI 2.33-
124.15) and quit attempt (defined as no smoking intentionally for at least 24 hours, 26% 
versus 12%, RR = 2.17, 95% CI 0.89-5.27) at 3-month follow-up. These findings have 
shown that using NRT sample to enhance quitting and using SC services is feasible and 
well accepted. However, due to the small sample size and wide confidence intervals of the 
trial results, the results hardly confirmed the effectiveness for the quitting outcomes. Also, 
the pilot study had not provided additional medication and other support, and had not 
referred the smokers to SC clinics, hence the 6-month quit rate was low (about 8%). 
8. Study design 
The proposed project has 4 phases: (1) Training of SC ambassadors (SCAs) for the SC 
promotion; (2) SC promotion sessions to deliver the medication counselling and NRT 
sampling (experimental group), or the advice to use NRT only (control group); (3) Follow-
up of the recruited smokers; (4) Evaluation of the effectiveness of training, promotions, and 
use of NRT sampling. To examine the effectiveness of NRT sampling for recruitment and 


NRT_protocol_v4 
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quitting, a multi-site cluster RCT (allocation ratio 2:1) will be used. All promotion sessions 
will be randomly allocated to either the experimental or the control group. The experimental 
group will receive medication counselling and NRT samples, while the control group only 
receive the advice to use NRT. Because smokers who receive NRT sampling will be more 
likely to participate in the study, the experimental sessions will then recruit more smokers 
than the control sessions. Hence, the allocation ratio of participants is arbitrarily set at 2:1. 
To increase comparability between the two groups, the promotion sessions of one hotspot 
will be randomly allocated to either group. All recruitment and quitting outcomes in the 
smokers between the experimental and control group will be compared.  
9. Subjects 
Smokers with the following inclusion criteria will be invited to participate in our RCT: (1) 
Hong Kong residents, (2) aged 18 to 65 years, (3) have used any tobacco products in the 
past month, (4) able to read and speak Chinese, (5) have not used NRT for the past month, 
(6) no severe angina, serious cardiac arrhythmias and hypertension, (7) have not suffered 
acute myocardial event in the past 4 weeks, (8) neither pregnant nor breastfeeding, (9) not 
under medication and treatment due to mental illness. To confirm the smoking status, in 
those who use conventional cigarettes, smokers’ exhaled carbon monoxide will be 
measured on-site. Nurses on truck will measure the blood pressure if smoker is aged over 
50 years old, obese by observation, or upon patient requests.  
10. Procedures 
In the experimental sessions, the SCAs will approach and distribute souvenirs (e.g. a pen) 
or leaflets to the smokers at outdoor smoking hotspots for 3-4 hours. The souvenirs and 
leaflets will have SC messages, quitline number and other SC services. If a smoker is 
willing to accept them and talk to the SCAs, the SCAs will advise the smoker to quit using 
the AWARD protocol. The AWARD protocol includes (1) Ask the smoking history, (2) 
Warn about the high risk (i.e., half of the smokers will die of smoking-related diseases), (3) 
Advise to quit, (4) Refer to the SC clinics of TWGHs and (5) Repeat the above advice (Do-
it-again) [4]. Our previous studies have shown that the AWARD protocol is a feasible and 
appropriate tool used by non-healthcare professionals to promote smoking cessation [4-6]. 
If the smoker is interested in using the SC services, the SCAs will introduce NRT to the 
smoker and conduct a preliminary assessment of his/her eligibility for enrolling in the 
“NRT sampling” programme. The SCAs will invite him/her to go to the smoking cessation 


NRT_protocol_v4 
Page | 9 
truck nearby to receive counselling by an onsite nurse. If the smoker is not eligible, he/she 
can still enroll in the cessation service provided by the SC clinics. 
11. Intervention: NRT sampling and medication counselling 
In the experimental sessions, an onsite nurse will assess whether each participant is fit for 
using NRT with further assessment on his/her current physical status, medication and blood 
pressure. If the participant is willing to use NRT to quit smoking and pass the nurse’s 
assessment, he/she will be prescribed the NRT sample, regardless of whether they use NRT 
for smoking reduction and when the quit day is. The nurse will help the participant decide 
which type of NRT product (gum: 2mg, patch: 14mg or 21mg) that he/she can use and 
advise him/her on how to use the NRT based on his/her smoking habit and daily cigarette 
consumption. In addition, the nurse will deliver medication counselling which addresses 
five main components: (1) the benefits for using NRT in quitting, (2) withdrawal symptoms 
due to smoking cessation, (3) side effects of NRT, (4) instructions for using NRT, and (5) 
making appointments for TWGHs SC clinics. Afterwards, the participant will receive 1-
week free NRT and an instruction card about the use of NRT. 
In the control sessions, all the above procedures for the experimental group will be applied, 
except that they will not receive an NRT sample and an instruction card about the use of 
NRT. Instead, they will be advised to obtain free NRT by enrolling in the SC clinics. Both 
groups will receive a one-page leaflet provided by the SC clinics.  
As this trial is a pragmatic trial, flexible procedures will be adopted based on the actual 
interaction with the participant. Firstly, the intervention components and filling in of 
baseline questionnaire may be carried out prior to seeking the consent from the participant 
if it is deemed more suitable in the situation and can make the procedures run more 
smoothly. Secondly, if the recruitment venue is not suitable for drug dispensing, the NRT 
sample and the use instructions will be register-mailed to the participants’ address instead 
of given immediately. All NRT will be prescribed by registered nurses. The research 
assistant will also contact the participants to confirm that they have received the NRT. This 
arrangement of mailing the NRT sample complies with the Pharmacy and Poisons 
Ordinance of the Drug Office. 
12. Randomization 


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We will use cluster randomization based on promotion session as the cluster unit because 
the procedures of individual randomization are difficult in outdoor areas as found in our 
pilot RCT. The PI will randomly allocate the promotion sessions within a hotspot to the 2 
groups by a list of group allocation which is based on a list of random numbers from Excel 
programme. Each hotspot will have 2 or more promotion sessions, and each session will 
last for about 3-4 hours. If a hotspot has 2 promotion sessions on 1 single day, the 2 sessions 
will be allocated into the same RCT group, and we will organize 2 more promotion sessions 
in this hotspot on another day. 
13. Allocation concealment 
All recruitment staff will know the group allocation before each promotion session, so no 
group concealment can be done. 
14. Blinding 
Participants cannot and will not be blinded to the intervention. Assessors of the follow-up 
outcomes and the research analysts will not be involved in the recruitment and intervention 
delivery, and will be blinded to the group allocation (single blindness). 
15. Follow-up 
All the smokers who consent to the follow-up will be contacted via telephone or WhatsApp 
around one week by a nurse or a research assistant after recruitment. The aim of this follow-
up is to enquire if there is any progress towards cessation and encourage the use of NRT 
and/or enrollment in SC services. 
At 1-, 3- and 6-month follow-up, the quitting outcomes will be assessed by a trained 
interviewer through telephone who is blinded to the subject’s group status. 
15.1 Intervention Group 
15.1.1 Participants who receive NRT samples and whose quit day is within one week after 
baseline 
A TWGHs nurse who is experienced in delivering smoking cessation will contact the 
participants around one week after baseline. The nurse will provide more intensive 
counseling to the smoker, especially on the use of NRT. All the smokers will be asked if 


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they have used any NRT and have any difficulties in using NRT, and will be given more 
counseling via telephone if necessary. 
15.1.1.1 Participants who have used NRT  
The TWGHs nurse will encourage him/her to obtain additional free NRT by enrolling in 
the SC clinics for the continuation of NRT use. If the smoker is unwilling to enroll, the 
nurse will advise him/her to purchase NRT over-the-counter. Other SC services will also 
be introduced or referred if the participant wants more other services. 
15.1.1.2 Participants who have not used NRT but is willing to use later 
The TWGHs nurse will advise him/her to use as soon as possible and invite him/her to 
receive one more follow-up within 1 month as long as the smoker provides the contact 
number and agrees to be contacted.  
15.1.1.3 Participants who show no interest to quit 
The TWGHs nurse will use the “5R” approach to re-motivate the quitting intention. The 
“5R” approach is being adopted by the local and international smoking cessation guideline 
including the discussion on why quitting is important (relevance), hazards of smoking (risk), 
benefits of quitting (rewards), difficulties (roadblocks) and repeated quit attempts 
(repetition).  
15.1.1.4 Participants who have contra-indication(s) to NRT 
If the smoker tells the nurse that he/she has contra-indication(s) to NRT, the nurse will 
advise him/her to stop using NRT to avoid risks.  
15.1.1.5 Participants who continue smoking during the use of NRT 
If the smoker has a dual use of cigarettes and NRT, the nurse will advise him/her to stop 
using NRT to avoid overdose. 
15.1.2 Participants who receive NRT samples and whose quit day is more than one week 
after baseline 
The research assistant will contact the participants around one week after baseline. The 
participants will receive motivational messages to encourage them to quit and enroll in the 


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SC clinics if they have not. They will also be asked if they need to contact the TWGHs 
counsellors for early cessation support. Otherwise, the participants will be contacted by the 
TWGHs nurse around one week after their quit day as outlined above in section 15.1.1. 
15.1.3 Participants who do not receive NRT samples but make an intake appointment 
within one week after baseline 
A TWGHs nurse will contact the participants within one week after baseline reminding 
them to attend the intake session. The nurse may contact some participants via phone for 
provision of further counselling or encouragement if necessary.  
15.1.4 Participants who do not receive NRT samples but make an intake appointment 
more than one week after baseline 
The research assistant will contact the participants around one week after baseline. The 
participants will receive motivational messages to encourage them to quit. They will also 
be asked if they need to contact the TWGHs counsellors for early cessation support. The 
participants will receive reminder message from the TWGHs nurse before their intake 
appointment. 
15.1.5 Participants who do not receive NRT samples and do not make an intake 
appointment  
The participants will receive motivational messages from the research assistant around one 
week after baseline to encourage them to quit and enroll in one of the SC clinics.  
15.2 Control Group 
15.2.1 Participants who make an intake appointment within one week after baseline 
A TWGHs nurse will message the participants within one week after baseline reminding 
them to attend the intake session. Meanwhile, the nurse may contact some participants via 
phone for provision of further counselling or encouragement if necessary.  
15.2.2 Participants who make an intake appointment more than one week after baseline 
The research assistant will contact the participants around one week after baseline. The 
participants will receive motivational messages to encourage them to quit. They will also 


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be asked if they need to contact the TWGHs counsellors for early cessation support. The 
participants will receive reminder message from the TWGHs nurse before their intake 
appointment. 
15.2.3 Participants who do not make an intake appointment  
The participants will receive motivational messages from the research assistant around one 
week after baseline to encourage them to quit and enroll in one of the SC clinics.  
 
16. Indicators and targets 
Our targets will be as follows: 
1. Train 40 tertiary students to be SCAs 
2. Deliver brief SC advice to 2,400 smokers (1,200 in the experimental and 1,200 in the 
control group) 
Experimental group 
3. Provide NRT sample to 720 smokers (60% of all the approached smokers), who also 
consent to the follow-up  
4. Motivate 288 smokers (40%) to use any SC services  
5. Motivate 144 smokers (20%) to attempt quitting (intended abstinence for at least 24 
hours).  
Control group 
6. 360 smokers (30% of all the approached smokers) will consent to the follow-up. 
7. Motivate 72 smokers (20%) to use any SC services  
8. Motivate 28 smokers (8%) smokers to attempt quitting  
Both groups 
9. 108 smokers report abstinence (for the past 7 days) at 6-month follow-up (30% of all 


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the 360 smokers who use any SC services) 
 
17. Sample size determination 
To detect a significant difference of the rate of quit attempt (20% versus 8%) with normal 
test and a power of 95% and 5% significance level, we need 485 subjects in the RCT 
(allocation ratio 2:1; 323 vs 162). Based on the method of Eldridge et al. (2006) [26], 
conservatively assuming that we could recruit 8 participants per session on average and the 
intra-cluster correlation coefficient was 0.1, the design effect is estimated to be 1.7. Thus, 
the minimum sample size required for the trial is 825 (=1.7 X 485) participants and 60 
sessions in total. With the similar calculation, the required sample size for detecting a 
significant difference in the proportion of using any SC service is 421. Therefore, our 
targeted sample size is sufficient to answer the research question. 
18. Data analyses 
To assess the change of knowledge, attitude and practice of SC due to the participation of 
the SCA workshop, all the outcomes will be tested by McNemar’s test (binary outcomes) 
and pair-sample t-test (continuous outcomes).  
To assess the effect of NRT sampling to the recruitment outcomes, the number of smokers 
who accept the brief advice or consent for the trial in each promotion session will be the 
outcome variables of Poisson regression model, with group allocation as the predictor, and 
total number of approached smokers in that promotion session as the offset variable.  
To compare the two primary quitting outcomes (binary) between experimental and control 
group, generalized estimating equations model will be used. Other secondary outcomes will 
be analyzed with either generalized estimating equations models (binary outcomes; e.g. 
tobacco abstinence) or linear mixed model (continuous outcomes; e.g. perceived 
importance to quit smoking).    
Cost analysis will be conducted to assess if the intervention is cost-effective, as what we 
did in our published paper [5]. Direct operating costs included salary (of training personnel, 
research assistants and SCAs), recruitment, telephone follow-up and publicity items. The 
total operation costs for the experimental group will include the cost for NRT sampling. 
Costs for study design, venues for training (provided by HKU), analysis, report writing and 


NRT_protocol_v4 
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irrelevant administration were excluded. In each group, the cost per successfully recruiting 
a smoker to receive any SC service was calculated by dividing the total cost by the number 
of smokers who report use of any smoking cessation. Similarly, the costs per quit attempt 
will also be calculated.


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19. Time-line: 
 
2018 
2019 
2020 
 
7 
8 
9 
10 
11 
12 
1 
2 
3 
4 
5 
6 
7 
8 
9 10 
11 
12 
1 
2 
3 
4 
5 
6 
HCPS – NRT sampling 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Development of the intervention, 
instruments and protocol 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Site selection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitment of ambassadors 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Training for staff, ambassadors and 
nurses  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject recruitments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3-day / 1-month follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3-month follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6-month follow-up (+validation) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6-month follow-up for SCAs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data entry and cleaning 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Report preparation  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Study protocol - Version v4, dated 7 May 2019 
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20. Describe any unusual or discomforting procedures to be used: Nil. 
21. Are there any hazards associated with the investigation? 
No.  
22. Ethical and legal issues 
According to the Drug Database of the Drug Office under Department of Health 
(http://www.drugoffice.gov.hk/eps/do/en/consumer/search_drug_database.html), all 
NRT products (in all forms and dosages) are classified as Part 2 Poisons and are 
referred as over-the-counter medicines. All Part 2 Poisons are regulated by the 
Pharmacy and Poisons Ordinance (Cap. 138). Accordingly, Part 2 Poisons can be sold 
in a pharmacy (ASP) or a medicine (LSP). They can also be supplied for the purpose 
of medical treatment by a person, who is not necessarily a medical practitioner, who 
practices medicine in a clinic registered in the Medical Clinics Ordinance. 
The present proposal targets to deliver a 1-week of free NRT to the smokers at the 
outdoor smoking hotspots, so that the smokers can obtain and use them as soon as 
being motivated to quit. To fully comply with the Ordinance, our collaborator (Tung 
Wah Group of Hospitals) has already registered a license from the Pharmacy and 
Poisons Board for their smoking cessation truck, which can park nearby the outdoor 
hotspots, so that our registered nurses can legitimately prescribe NRT to the recently-
recruited smokers in this truck. The truck is a mobile clinic which can provide brief 
counseling sessions and medications like a clinic. The student ambassadors will 
mainly be responsible to approach the smokers at the hotspots and invite them to 
receive advice and NRT in the truck.  
Other measures will also be undertaken to protect the participants: (1) Our intervention 
will include a brief advice about how to correctly use the NRT, side effects and other 
safety measures. Hence, our intervention is even safer than smokers buying over-the-
counter NRT from pharmacy without any advice. (2) Only registered nurses will be 
responsible to provide NRT to the participants. (3) All on-site documentations will be 
locked in a cabinet of the truck, and handled carefully by the project coordinators. We 
will strictly follow the data security guideline under the University of Hong Kong. (4) 


Study protocol - Version v4, dated 7 May 2019 
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Participants who do not meet the inclusion criteria will be suggested to meet the 
physicians in the smoking cessation clinics and obtain the medication advice from the 
physicians before using NRT. They will not be included in this trial. This will help 
ineligible participants to use NRT safely. (5) The pilot study of the present proposal 
was fully reviewed and approved by the Institutional Review Board (IRB) of the 
University of Hong Kong / Hospital Authority Hong Kong West Cluster (Ref: UW 15-
232). Therefore, our procedures and interventions met the ethical requirement and 
protect participants’ privacy. We have already submitted the IRB application for the 
present study. The recruitment will only start when the research is approved by the 
IRB.  
23. Direct access to source data/documents 
The raw data will be stored in the CD-ROM and locked in a cupboard with keys kept 
by the Principal Investigator. Only the Investigators and Research Assistant of the 
project will be permitted to access to raw data and/or study record. The data will be 
kept for 10 years or longer after the study completed.  
24. Dissemination of study result 
The research findings will be disseminated through publication in international peer 
reviewed journals including American Journal of Health Promotion and Nicotine & 
Tobacco Research. Papers will also be presented in international conferences such as 
(1) the Annual Scientific Meeting of the Society on Research on Nicotine and Tobacco 
(SRNT); national conferences such as (2) the Asia Pacific Conference on Tobacco or 
Health and Cross-strait Conference on Tobacco Control (China, Hong Kong, Macau 
and Taiwan); and (3) regional conferences in Mainland China and Hong Kong.  
25. Consent 
Eligible participants will be invited to participate in the study by obtaining written 
consent.   
26. Conflict of interest: None 


Study protocol - Version v4, dated 7 May 2019 
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27. Financing and insurance 
This research is funded by Health and Medical Research Fund of the Food and Health 
Bureau. 
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