Tobacco cessation intervention for individuals with severe mental illness in Bangladesh, India, and Pakistan: protocol for a multi-country feasibility randomised controlled trial (SCIMITAR-SA)

Mental disorders are a major contributor to the global disease burden, ranking among the top ten causes of health loss worldwide [1]. Individuals with Severe Mental Illness (SMI) (Schizophrenia, Schizoaffective disorder, Psychosis, Bipolar illness and Severe Depression with/without psychosis) represent one of the most vulnerable population groups [2]. They face pronounced health disparities, physical multimorbidity [3], higher mortality, shorter life expectancy, driven by both biological and behavioural factors such as smoking, poor diet, drug use, and inactivity [[3], [4], [5]]. Tobacco consumption is a major modifiable cause of morbidity and mortality, resulting in more than seven million deaths annually and contributing to prolonged disability and suffering from tobacco-related conditions [6].

Around two in three individuals with SMI are current smokers [7] and reducing tobacco use in this group is recognised as an effective strategy to narrow the life expectancy gap [8]. South Asian LMICs, particularly Bangladesh, India, and Pakistan bear the highest burden of tobacco-related disease, encompassing both smoking and smokeless tobacco (SLT) [[9], [10], [11]]. While data from the region are limited, smoking prevalence as high as 50% among individuals with SMI [12], and widespread use of SLT in the general population [13] is reported. Despite population-level declines in tobacco use over the past four decades, little reduction has occurred among individuals with SMI [14,15]. A multi-country survey in Bangladesh, India, and Pakistan reported higher tobacco use among people with SMI, especially men, yet only 38.4% had received advice to quit [16].

Although individuals with SMI are often motivated to improve their physical health, including quitting tobacco, they require tailored cessation support due to complex treatment regimens, higher dependence, and the need for psychotropic medication adjustment, differing literacy levels, cognitive difficulties, medication affecting self-efficacy and motivation [[17], [18], [19]].

Evidence from high-income countries, notably the UK SCIMITAR trial, has demonstrated that SMI-specific interventions significantly increase quit rates, improve quality of life, and are cost-effective [17].

However, these findings cannot be directly translated to LMICs, where tobacco consumption varies and includes non-cigarette products (bidi and hookah) and SLT products, and where health system capacities, cultural norms, and resource contexts differ substantially [[18], [19], [20], [21]]. No large-scale, contextually adapted cessation trials for individuals with SMI exist in these settings, representing a critical evidence gap [22,23]. Conducting a feasibility trial is therefore essential to assess intervention acceptability, relevance, and operational practicality of its delivery, and to enable refinement of our approach to its integration within the diverse contexts before evaluating effectiveness in a definitive trial [[24], [25], [26]]. The Smoking Cessation Intervention for Severe Mental Ill Health–South Asia (SCIMITAR-SA) has been adapted from the UK National Centre for Smoking Cessation and Training (NCSCT) Standard Treatment Programme [27], drawing on evidence from two South Asian cessation trials, IMPACT4S (smoking cessation support for people with SMI) [28] and ASTRA (SLT users) [29], and expanded to support dual tobacco users. Adaptation involved community engagement and involvement workshops, pre-testing with individuals with SMI and intervention delivery staff, and stakeholder consultations across Bangladesh, India, and Pakistan to guide context-specific modifications. SCIMITAR-SA follows a patient-centred approach, tailoring support and promoting autonomy in culturally aligned cessation choices, and aims to address this gap through a feasibility randomised controlled trial across Bangladesh, India, and Pakistan to lay a robust groundwork for a future definitive trial and strengthen broader efforts toward tobacco control in this population.

The feasibility trial protocol is prospectively registered (ISRCTN91038721) and adheres to SPIRIT checklist and CONSORT guidelines [30].

Participants will be randomly allocated to the intervention or control arm using consecutively numbered, sealed opaque envelopes. The randomisation schedule will be generated by a statistician at the York Trials Unit (YTU) using Stata (version 19) [37] with stratified block randomisation by site and tobacco-use type (smoked only, smokeless only, or dual users), employing variable block sizes of two and four. Each allocation will be printed on a card, sealed in an envelope, and labelled sequentially according to the schedule. Envelopes will be securely stored at each site and accessed only by authorised staff. Following baseline data collection, the RA will contact a trial coordinator at the central research office, who will open the next envelope, record the allocation, and inform the RA. The RA will document the allocation in the baseline e-CRF and notify participants. The coordinator will inform the TDA of intervention-arm participants to schedule intervention sessions.

Web-based or REDCap randomisation will not be used due to unreliable internet connectivity across participating outpatient facilities, which could compromise real-time allocation during clinic workflows. Sealed opaque envelopes will therefore be used as a pragmatic and robust approach suitable for multi-country implementation in these settings. Envelope integrity will be monitored through central oversight, sequential numbering, secure storage, and regular cross-checking of allocation logs against the master randomisation schedule.

After recruitment, data will be collected from participants, with or without the support of caregivers, at baseline (after informed consent and prior to randomisation) and at four and seven months post-randomisation. The trained RAs will administer all instruments in person using REDCap [36] on electronic tablets. Participants in the intervention arm will have a 30-day grace period to set their first quit date, and all follow-up assessments will take place at four and seven months after randomisation.

At baseline, data will be obtained on socio-demographic characteristics (age, gender, education, occupation, marital status, and household assets to determine socioeconomic status using items from the ASTRA trial) [38] and diagnosis of SMI confirmed through the Quick SCID [39]. The psychiatric symptom severity will be assessed at baseline and seven months using the Brief Psychiatric Rating Scale (BPRS) [40]. The history of tobacco use (age at initiation, type, frequency, duration, and prior quit attempts) will be collected using items adapted from the ASTRA [38], Quit4TB and IMPACT-4S [28] trials. Nicotine dependence will be measured using the adapted Heaviness of Smoking Index from ASTRA trial [38], withdrawal symptoms using the Mood and Physical Symptoms Scale (MPSS) [41] and motivation to quit through the Motivation to Quit (MTQ) questionnaire [42]. The EQ-5D-5L [43] will assess health-related quality of life(HRQoL), while the PHQ-9 [44], GAD-7 [45], and SF-12 [46] will measure depressive and anxiety symptoms and physical and mental health status, respectively.

At four months follow-up, data collection will focus on tobacco-use outcomes, nicotine dependence, withdrawal symptoms, health-related quality of life, mental and physical health, health-service utilisation, and anthropometric measures. Specifically, tobacco-use status since the quit date and in the previous week will be assessed using items from the ASTRA trial [38], including any use of nicotine products (such as e-cigarettes or nicotine oral pouches). Nicotine dependence will be measured using the adapted Heaviness of Smoking Index from ASTRA trial [38], withdrawal symptoms using the Mood and Physical Symptoms Scale (MPSS) [41]. The EQ-5D-5L [43] will assess health-related quality of life(HRQoL), while the PHQ-9 [44], GAD-7 [45], and SF-12 [46] will measure depressive and anxiety symptoms and physical and mental health status, respectively. Health-service use and out-of-pocket expenditures will be captured using a questionnaire adapted from previous trials (ASTRA [38], POTENTIAL [47], and RESPIRE [48]) and height and weight will be recorded to calculate BMI following WHO protocols [49].

At seven months follow up, all measures from the four-month assessment and BPRS will be repeated, and an additional salivary sample will be collected to biochemically verify abstinence. We will operationalise the biochemically verified continuous abstinence from all tobacco products using the global Russell Standard of sustained and verified quitting [50]. For those who report using tobacco products on no more than 5 occasions during the cessation period (duration between the target quit date (for intervention group) or 30 days post-randomisation (for the control group) and the seven month follow up time point) at the seven-month follow-up, biochemical verification will be carried out through salivary cotinine and Anabasine testing through LC-MS (ACM Global Laboratories, UK for Bangladesh and Pakistan & Laboratory of the Department of Clinical Psychopharmacology and Neurotoxicology for India). Cotinine level <15 ng/ml will be used to identify biochemically verified abstinence), whereas those who self-report continuous abstinence but have cotinine levels above the threshold will be identified as tobacco users. Biochemically verified tobacco abstinence at seven months is included as an exploratory outcome to assess the feasibility of collecting cessation outcome data, including biochemical verification, and to inform outcome selection, measurement procedures, and sample size estimation for a future definitive trial.

Follow-up assessments at four and seven months post-randomisation will be considered on time if completed within a one-week window before or after the scheduled date. RAs will begin contacting participants one week prior to, and for up to three weeks after, each due date, making up to three phone calls per week at varying times and days to schedule the assessment. Instances of delayed follow-up will be documented and reviewed after the feasibility phase to refine procedures for the main trial. If the four-month data are missed, efforts will still be made to obtain information at the seven-month follow-up.

The study will report on the following feasibility outcome measures to address the research questions for the trial:

• i)
  Recruitment, retention, acceptability

  • 1.
    Recruitment rates, assessed as the number of participants eligible, consenting and randomised, out of those screened.
  • 2.
    Reasons for ineligibility/non-participation/non-consent of participants where provided.
  • 3.
    Retention in the study, assessed as the number of participants randomised who are successfully followed up at four and seven months post randomisation with details of withdrawals and loss to follow-up where available.
  • 4.
    Qualitative feedback from research staff, health facility staff and trial participants on trial processes
• ii)
  Intervention Delivery

  • 1.
    Retention in intervention reported as the total number of sessions attended out of the total number of sessions offered.
  • 2.
    Review of participant session records held by TDAs
  • 3.
    Qualitative feedback from TDAs, mental health facility staff and trial participants on delivery, implementation and receipt of the SCIMITAR-SA intervention.
• iii)
  Data completion

  • 1.
    Completeness of data for baseline assessments, outcome measures for the definitive trial and data on health resource use at four and seven months.
  • 2.
    Data completeness of self-reported and biochemically verified continuous abstinence from all tobacco products at seven months.

The SCIMITAR-SA feasibility trial will address a critical evidence gap by evaluating the feasibility of a culturally relevant behavioural intervention to support tobacco cessation among individuals with SMI in South Asia. This population faces high rates of tobacco dependence and significant barriers to cessation, yet tailored, evidence-based support remains limited. The study’s participant-centred approach integrates cessation support for smokers, smokeless tobacco (SLT) users, and dual users, combining behavioural intervention with optional NRT (where available as part of routine care) delivered within existing mental health services.

A major strength of the study lies in its multi-country implementation across diverse health-system contexts in Bangladesh, India, and Pakistan, using consistent, validated tools and a robust data-collection framework. The inclusion of qualitative process-evaluation components adds depth to understanding contextual barriers and facilitators of implementation. Moreover, the focus on integrating cessation support into routine psychiatric care highlights the feasibility of sustainable delivery models.

However, as a feasibility study with a modest sample size, it is not powered to detect significant differences in effectiveness outcomes. Other limitations include potential variability in NRT availability across sites, challenges in retaining a highly clinically vulnerable population, and possible under-reporting of tobacco use due to social desirability bias. Despite these constraints, SCIMITAR-SA provides an essential foundation for a definitive trial and strengthens the evidence base for integrating tobacco cessation into mental health care in low- and middle-income settings.

Garima Bhatt: Writing – review & editing, Writing – original draft, Project administration, Conceptualization. Kousar Ishaq: Writing – review & editing, Project administration, Investigation, Conceptualization. Aatik Arsh: Writing – review & editing, Resources, Project administration, Methodology, Conceptualization. Omara Dogar: Writing – review & editing, Visualization, Resources, Funding acquisition, Conceptualization. Justin Fenty: Writing – review & editing, Validation, Formal analysis, Conceptualization. Cath Jackson: Writing – review & editing, Resources, Conceptualization. Muqaddas Asif: Writing – review & editing, Resources, Investigation, Conceptualization. Jothisha C: Writing – review & editing, Resources, Investigation, Data curation, Conceptualization. Shannon Halmkan: Writing – review & editing, Validation, Formal analysis, Data curation, Conceptualization. Fahmida Islam: Writing – review & editing, Resources, Investigation, Conceptualization. Krishna Prasad Muliyala: Writing – review & editing, Methodology, Funding acquisition, Conceptualization. Venkata Lakshmi Narasimha: Writing – review & editing, Resources, Funding acquisition, Conceptualization. Steve Parrott: Writing – review & editing, Visualization, Funding acquisition, Conceptualization. Rebecca R: Writing – review & editing, Resources, Investigation, Conceptualization. Fahmidur Rahman: Software, Data curation, Conceptualization. Faraz Siddiqui: Writing – review & editing, Supervision, Methodology, Funding acquisition, Conceptualization. Heather Thomson: Writing – review & editing, Resources, Conceptualization. Han-I Wang: Writing – review & editing, Conceptualization. Rumana Huque: Writing – review & editing, Methodology, Funding acquisition, Conceptualization. Imran B. Chaudhry: Methodology, Funding acquisition, Conceptualization. Asad Tamizuddin Nizami: Methodology, Funding acquisition, Conceptualization. Catherine Hewitt: Visualization, Methodology, Funding acquisition, Conceptualization. Najma Siddiqi: Writing – review & editing, Supervision, Project administration, Methodology, Conceptualization. Kamran Siddiqi: Writing – review & editing, Supervision, Project administration, Methodology, Funding acquisition, Conceptualization. Simon Gilbody: Visualization, Supervision, Project administration, Methodology, Conceptualization. Pratima Murthy: Visualization, Supervision, Methodology, Funding acquisition, Conceptualization.

Not applicable.

The feasibility trial protocol has been approved by the Health Sciences Research Governance Committee (HSRGC) at the University of York (Ref: HSRGC/2024/626/E: SCIMITAR-SA), National Research and Bioethics Committees in Bangladesh (National Research Ethics Committee (NREC) functioning under Bangladesh Medical Research Council (BMRC)), (Ref: BMRC/NREC/2025-2027/128), Health Ministry’s Screening Committee (HMSC) operated by the Department of Health Research/Indian Council of Medical Research (ICMR)) and the Screening Committee for Research Proposal (SCRP), Department of Health and Family Welfare, Ministry of Health and Family Welfare, Government of India (Ref: F.No P- 29010/19/2025-DMCell), Ethics Committee (Behavioural Science Division) of National Institute of Mental Health and Neurosciences, Bengaluru, India, (Ref: NIMHANS/47th IEC (BEH.SC.DIV.)/2024), National Bioethics Committee for Research (NBC-R) at Health Research Institute, National Institutes of Health (NIH)) in Pakistan (Ref: 4-87/NBCR-1145/24-25/1422), and Institutional Research & Ethics Forum (IREF), Rawalpindi Medical University (RMU), Rawalpindi, Pakistan (Ref: 810/IREF/RMU/2024). Any amendment to the protocol will be submitted for approval to the same ethics governing bodies in respective partner countries. The informed consent to participate in the feasibility trial will be obtained directly from the patient(s).

Not applicable.

The SCIMITAR-SA programme is funded by the National Institute for Health and Care Research [Grant reference: Research & Innovation for Global Health Transformation (RIGHT) NIHR205601] and is sponsored by the University of York, UK. The views expressed in the manuscript are of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care.