Use of Nicotine Replacement Therapy (NRT) Sample and Brief Smoking Cessation Advice for Recruiting Smokers
Condition: Smoking Cessation
Study type: Interventional

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
      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

      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 60 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.
    

Intervention name(s): Nicotine replacement therapy (NRT) sampling; Medication counseling
Intervention type(s): Drug; Behavioral
Intervention description(s): 1-week free NRT samples (patch or gum); Medication counseling
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: intervention; nicotine replacement sample; smoking cessation; smoking hotspots