Study type and design

This study is a cluster randomised controlled trial, with randomisation conducted at the clinic level to minimise contamination between participants. It will be implemented in four public primary care clinics in the Hulu Langat district. Clinics will first be categorised by setting (urban or suburban), and randomisation will be conducted within each category using a computer-generated sequence. Two clinics (one urban and one suburban) will be allocated to the intervention arm, where participants will receive the InTroDuce-Programme, and the remaining two clinics will serve as controls, providing standard antenatal care.

Study duration

The study duration is 24 months, from 15 July 2025 to 14 July 2027. The initial phase will involve research planning and development of the web-based educational module (InTroDuce-Programme), followed by trial implementation and effectiveness evaluation. Recruitment is anticipated to commence on 2 February 2026 and is expected to continue for approximately six months, until August 2026, subject to administrative and logistical approvals. At enrolment, baseline data (T0) will be collected for both intervention and control groups. Participants allocated to the intervention group will receive the educational module immediately after completion of the baseline assessment (T0) and will complete an immediate post-intervention assessment (T1) to evaluate short-term knowledge acquisition. A follow-up assessment at one-month post-intervention (T2) will be conducted for both intervention and control groups.

Data collection is expected to be completed by August 2026, with results anticipated by mid-2027. The schedule of enrolment, intervention, and assessments is outlined in Fig 1.

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Fig 1. Schedule of enrolment, intervention and assessment.

* Immediate post-intervention assessment conducted in the intervention group only. T0 = Baseline (pre-intervention); T1 = Immediate post-intervention assessment (intervention group only); T2 = One-month follow-up assessment. ‘X’ indicates when the activity or assessment occurs.

https://doi.org/10.1371/journal.pone.0344651.g001

Study location

The study will take place in four primary care clinics in Hulu Langat district, Selangor, Malaysia. Kajang Health Clinic and Bandar Baru Bangi Health Clinic represent urban sites, while Batu 9 Health Clinic and Balakong Health Clinic represent suburban sites. These were chosen to ensure a mix of geographic and demographic representation.

Study population

The study population consists of pregnant women attending the four participating clinics during the recruitment period.

Inclusion and exclusion criteria

Inclusion criteria:

1. Pregnant women aged 18 years and older.
2. At or before 27 weeks of gestation, ensuring that participants are recruited prior to the recommended vaccination window.
3. Able to understand and provide informed consent.

Exclusion criteria:

1. History of severe anaphylactic or allergic reactions to previous influenza or Tdap vaccination.
2. Non-Malaysian citizens

Sample size estimation

Sample size was calculated using OpenEpi software, based on O’Leary et al. (2019), which reported a 19% absolute difference in vaccine intention between intervention (55%) and control groups (36%) [20]. To detect this difference with 80% power and a 5% two-sided significance level, a total of 216 participants were required for an individually randomised design. As this is a cluster randomised trial, the sample size was adjusted for clustering using a design effect of 1.3, assuming an intracluster correlation coefficient (ICC) of 0.05. This ICC value was selected based on published cluster trials of educational and behavioural interventions in primary care, where ICCs for knowledge and intention outcomes are typically low (<0.05) [21]. Given the limited number of clusters (four clinics), the sample size supports a pragmatic, early-phase evaluation, and is not powered for definitive effectiveness conclusions. Findings are intended to inform the design of a future, fully powered trial. Allowing for 20% attrition, the final sample size is 351 participants (88 per clinic).

Sampling method and participant recruitment

Cluster randomisation will occur at the clinic level. Within each clinic, consecutive sampling of eligible pregnant women will be used until the target sample size is achieved. Research officers will screen women during antenatal visits, obtain informed consent, and enrol participants.

Research phases and tools

This protocol outlines the development, implementation, and evaluation of the InTroDuce-Programme, a web-based educational intervention designed to improve knowledge and future intention for influenza and Tdap vaccination among pregnant women. The study consists of two phases.

Phase 1: Development of the educational video module using the Health Belief Model (HBM).

The InTroDuce-Programme will be developed as a short, web-based video module (~7 minutes) to promote maternal vaccination. Its design will be guided by the HBM, targeting constructs such as perceived susceptibility, severity, benefits, barriers, and self-efficacy. To increase behavioural impact, the module will integrate simplified and empathetic messaging, visual storytelling, and culturally relevant content in Bahasa Melayu. Local issues, including vaccine myths (halal status), will be addressed in line with the Malaysian Maternal Immunisation Consensus Guidelines [22].

To address perceived barriers, particularly concerns related to vaccine safety and religious permissibility, the module includes messages such as: “Influenza and Tdap vaccines given during pregnancy are inactivated or subunit vaccines that do not contain live pathogens and are safe for both the mother and the baby.” In addition, the module states that “the use of influenza and Tdap vaccines during pregnancy is considered harus (permissible under Islamic law) when they are proven to be safe, contain no impermissible substances that remain, or when the original substances have undergone istihalah (complete chemical transformation), rendering the final product suci (ritually pure), and are used to protect life.” Clarification of “harus” status is relevant in the Malaysian context, where religious permissibility under Islamic jurisprudence may influence vaccine acceptance among pregnant women.

Message framing is differentiated according to maternal risk perception. Messages on pertussis (Tdap) emphasise protection of the newborn, reflecting the common perception that pertussis primarily threatens infants, particularly in early life. In contrast, influenza messages highlight protection of both the mother and the baby, acknowledging influenza as a health risk mainly perceived by pregnant women to affect themselves. This differentiated framing aligns message emphasis with maternal concerns and relevant HBM constructs to enhance message relevance and acceptability.

The development process will include:

1. Content and theory development: establishing key educational messages guided by the HBM.
2. Module drafting: preparing initial materials (text, audio, and visual) addressing all six HBM constructs.
3. Expert review and content validation: input from family medicine specialists, obstetricians, and public health experts to ensure accuracy and relevance.
4. Refinement: revisions based on expert feedback.
5. Pilot testing: evaluation with a small group of pregnant women (n = 20) will be conducted to assess feasibility and study flow. Face validation will be conducted with a subset of participants using a structured face validation form to assess clarity, user-friendliness, and engagement. Quantitative ratings and qualitative feedback will be reviewed by the research team, and identified issues will be addressed through revisions to content, visuals, and delivery before full trial rollout. Participants involved in pilot testing will not be included in the main trial.
6. Final refinement: adjustments based on pilot testing before full trial implementation.

The module will be deployed via a password-protected website accessible on smartphones.

Note: The InTroDuce-Programme explicitly incorporates HBM constructs to address key determinants of vaccination behaviour. Each module component aligns with a specific HBM construct to improve knowledge, address perceived barriers, and empower informed decision-making among pregnant women (see Table 1).

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Table 1. Mapping of health belief model constructs to the InTroDuce-Programme components.

https://doi.org/10.1371/journal.pone.0344651.t001

Data collection and instruments

Data will be collected at baseline (T0) and one-month follow-up (T2) for both intervention and control groups. Upon obtaining consent, the research officer will administer a baseline questionnaire via Google Form to collect sociodemographic and clinical data, knowledge, attitudes and vaccination intention. Participants in the intervention arm will then watch the video module during the same visit and will complete an additional immediate post-intervention assessment (T1), which will assess short-term knowledge acquisition. Both intervention and control participants will complete the follow-up questionnaire at T2. Fig 2 illustrates the CONSORT flow diagram for enrolment, allocation, follow-up and analysis.

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Fig 2. CONSORT flow diagram of enrolment, allocation, follow-up and analysis.

https://doi.org/10.1371/journal.pone.0344651.g002

Outcomes

Primary outcomes:

1. 1. Vaccination knowledge: Change in knowledge score from T0 to T2 based on correct responses to the knowledge items.
2. 2. Vaccination intention: Change in intention to receive influenza and Tdap vaccination during the current pregnancy from T0 to T2, measured via two items (Yes/No/Not sure) coded ordinally (No = 0, Not sure = 1, Yes = 2).

Secondary outcomes:

1. 3. Attitudes and perceived barriers: Scores on the six attitude items capturing constructs such as perceived susceptibility, severity, benefits, barriers, cues to action and self-efficacy.
2. 4. Factors associated with lower knowledge or intention: Associations between sociodemographic and clinical variables (e.g., age, parity, education, household income) and outcomes.
3. 5. Preferences for information sources and modes: Responses on preferred sources/modes of vaccine information (e.g., healthcare provider, WhatsApp, authorised website) to inform communication strategies.

Data analysis

Data will be analysed using IBM SPSS Statistics version 29. Participant characteristics will be described using descriptive statistics at both the individual participant level and the cluster (clinic) level, with categorical variables expressed as frequencies and percentages, and continuous variables summarised as means with standard deviations or medians with interquartile ranges, as appropriate. Missing data will be handled using complete-case analysis, with planned sensitivity analyses specified in the Statistical Analysis Plan. Given the small number of clusters (k = 4), the primary analysis will be conducted at the cluster level. For each clinic, summary measures will be calculated for the primary outcomes, including the mean change in knowledge score and the proportion of participants reporting positive vaccination intention. The intervention effect will be assessed by comparing these clinic-level summaries between intervention and control clinics using independent samples t-tests, which are intended as exploratory comparisons given the limited number of clusters and will be interpreted cautiously, with consideration of effect sizes and confidence intervals in addition to statistical significance.

Secondary exploratory analyses will be conducted at the individual level using Generalised Estimating Equations (GEE) with an exchangeable correlation structure to account for clustering and repeated measures. For continuous outcomes (knowledge scores), an identity link will be used; for ordinal intention scores, a cumulative logit link will be applied. Models will adjust for baseline values and prespecified covariates such as age and education. Findings from these analyses will be interpreted cautiously given the limited number of clusters. Exploratory logistic regression analyses will be conducted to examine factors associated with low vaccination intention at individual level. These analyses are intended to be descriptive and hypothesis-generating and will be interpreted cautiously in light of the small number of clusters.

Additional sensitivity analyses will be conducted to assess model stability, including comparison of unadjusted and covariate-adjusted models and consistency between cluster-level and individual-level exploratory analyses. Statistical inference will be interpreted in the context of the exploratory nature of the analyses, with emphasis placed on effect sizes and confidence intervals. A two-tailed p-value < 0.05 will denote statistical significance.

A detailed Statistical Analysis Plan will be finalised prior to outcome analysis and before access to outcome data. Reporting will follow the CONSORT 2010 extension for cluster randomised trials.

Data management

Data will be collected directly through Google Forms, which automatically records responses into a secure, password-protected Google Sheet. Built-in validation rules (e.g., mandatory fields, age limits) will minimise missing or out-of-range values. The research team will conduct regular quality checks to identify and correct inconsistencies. All study data will be stored in accordance with institutional and national data protection requirements on encrypted institutional servers, accessible only to authorised members of the research team. Personal identifiers (e.g., names and contact details) will not be included in the main survey dataset. Each participant will instead be assigned a unique study identification number, with the linkage file containing personal identifiers stored separately under restricted access. Data will be retained for seven years after study completion, in line with institutional policy, and will then be permanently deleted. De-identified datasets and analysis codes may be made available to qualified researchers upon reasonable request and approval from the relevant ethics committee and data custodians.

Ethics approval, trial registration, and consent to participate

The study received ethical approval from the Medical Research and Ethics Committee, Ministry of Health Malaysia, through the National Medical Research Registry (NMRR ID: 25-00625-ECZ (IIR)); approval date: 22 April 2025. The approval is valid until 21 April 2026, and an extension will be requested if required. The protocol approved by the Medical Research and Ethics Committee is provided in S1 Protocol. It is registered with ClinicalTrials.gov (NCT06815250; 7 February 2025). Permission will be obtained from the state health department and district office before data collection. The trial will be conducted in accordance with the Declaration of Helsinki and the Malaysian Guidelines for Good Clinical Practice. Any important protocol amendments will be submitted for prior approval to the ethics committee and updated in the trial registry. Relevant changes will also be communicated to investigators, reported in the final manuscript, and disclosed to journal editors at submission. Participants will be informed about the study during routine clinic visits. Written informed consent will be obtained from all participants prior to enrolment and will be documented electronically. The consent process will provide participants with the full information sheet and require active acknowledgement before submission. No minors will be included. A token of appreciation (Ringgit Malaysia 30) will be provided upon completion of the study. The patient information sheet and informed consent form are provided in S1 Appendix.

Safety considerations

The intervention involves only an educational module and questionnaires, posing minimal risk. Potential discomfort is limited to the time spent answering questions. Participants may withdraw at any time without impact on their usual care.

Privacy and confidentiality

Personal identifiers will be kept in a separate, password-protected file accessible only to the principal investigator and data manager. Only study IDs will appear on questionnaires and datasets. No personal information will be included in reports or publications.

The complete SPIRIT checklist is provided in S1 Checklist.

Dissemination plans

Findings will be disseminated through national and international conferences and submissions to peer-reviewed journals on public health, vaccination, primary care, and maternal health. Key results will be shared with policymakers, maternal health programme managers, and frontline healthcare providers through summary reports and presentations to support evidence-based decision-making. The InTroDuce-Programme may also be adapted for practical use in antenatal classes and clinic waiting areas to extend its reach. The full protocol and analysis plan will accompany the final publication. De-identified data may be shared in line with data management procedures.

Strength and limitations

This study is among the first in Malaysia to evaluate a web-based educational module on maternal vaccination, employing a cluster randomised controlled design to minimise contamination. Its digital format is scalable and feasible for integration into routine antenatal care. Analyses of barriers and sociodemographic factors will provide valuable insights to guide targeted interventions. Limitations include the lack of participant blinding, which may introduce response bias; the relatively short follow-up period, which may not capture long-term uptake; and reliance on self-reported intention rather than verified vaccination. This study primarily assessed changes in knowledge and behavioural intention rather than verified vaccine uptake. Although confirmed uptake would represent a more definitive measure of effectiveness, this was not feasible within the scope of the current protocol due to the timing of national Tdap implementation and resource constraints. It is acknowledged that willingness or intention to receive vaccination may not necessarily translate into actual vaccine uptake. Intention was therefore selected as a pragmatic and theoretically grounded outcome, and future studies should evaluate the impact of the intervention on confirmed vaccination uptake.

Intervention delivery involved monitoring by research assistants to ensure fidelity, which may not fully reflect routine clinical practice where such supervision is unlikely. The intervention was designed as a brief, standalone video, allowing flexibility for future dissemination through routine channels, such as display in healthcare facility waiting areas, although the effectiveness of such approaches in rural or low digital access settings was not evaluated in this study. In addition, the small number of clusters limits statistical efficiency and the precision of cluster-level effect estimates. As the primary cluster-level analyses are exploratory in nature, findings will be interpreted cautiously, with emphasis placed on effect sizes and confidence intervals rather than statistical significance alone. The intracluster correlation coefficient assumed for sample size estimation was based on published primary care trials, and ICC values may differ in Malaysian primary care settings, which could affect the precision of effect estimates. The sample size calculation was also informed by a single published study conducted in a high-income setting, which may limit the generalisability of the assumed effect size to the local context. Finally, some residual cross-clinic contamination is possible despite randomisation at the clinic level. Although clinics were located at least 10 km apart and participants in the intervention group were reminded not to share the module with others, sharing of digital content cannot be fully controlled during the study period.

Termination of study

The study may be terminated at any time at the discretion of the investigators. If termination occurs, participants will be notified promptly, and follow-up arrangements will be made as appropriate.