This study is a stratified cluster RCT designed to evaluate the effectiveness of FV in preventing dental caries among students attending special education schools in Guangdong Province, China. This trial is open label. Neither participants, caregivers, nor outcome assessors will be blinded to group allocation due to the nature of the intervention.

All special education schools located in Guangdong Province are eligible for inclusion if they provide primary and/or secondary education to students with disabilities. No minimum enrollment threshold is required, and schools are not excluded based on size or student composition. All participating institutions are formally registered educational entities operating under the supervision of local education authorities. According to the Guangdong Provincial Education Bureau, there are a total of 162 special education schools distributed across 21 prefecture-level cities. Cities such as Guangzhou (n=19, 11.7%), Shenzhen (n=11, 6.8%), and Shantou (n=8, 4.9%) have relatively higher concentrations of eligible schools. The sampling frame for this trial was constructed using the official registry of special education schools.

Guangzhou, representing a high economic development region within the Pearl River Delta along with Yunfu and Heyuan, which represent middle-to-low development regions from western and northern Guangdong, respectively, were purposively selected to ensure geographic and socioeconomic diversity. Within each of these 3 cities, eligible schools were identified from lists of schools willing to participate provided by local education authorities. School-level cluster randomization was then performed stratified by city. A computer-generated random allocation sequence was produced by an independent statistician who was not involved in school recruitment, baseline assessment, or intervention implementation. Schools within each city were randomly assigned to either the intervention or control group according to this sequence. To ensure allocation concealment, opaque, sealed envelopes containing group assignments were prepared by staff not involved in intervention implementation. Allocations will be disclosed only after completion of school enrollment. Ultimately, 5 control schools and 7 intervention schools were selected across the 3 cities to participate in the study (Figure 1).

Students enrolled in participating schools will be recruited, with informed consent obtained from their legal guardians.

Students will be excluded if they have bronchial asthma, a known severe allergy or hypersensitivity to FV. They will also be excluded if they have acute oral conditions or severe systemic diseases. Students who are unable to cooperate or refuse to participate in the study will also be excluded.

The primary outcome of this study is the prevalence of dental caries at 12 months. On the basis of previous literature in comparable populations, the prevalence of caries among students in special education schools without intervention is estimated at 60% [5,14]. A reduction to 40% in the intervention group is considered clinically and politically meaningful [9,15]. Using a 2-sided α of .05 and a power of 90% (β=.10), the required sample size per group for an individually randomized trial is estimated using the formula:

where z_α/2 is 1.96, Z_β is 1.28, p₁ is 0.60, and p₂ is 0.40. Substituting these values gives a sample size of approximately 126 per group under individual randomization. Additionally, this study uses a stratified cluster RCT design, which requires adjustment for clustering using the design effect. The design effect was calculated as 1+(m–1)×ρ where m=150 (average cluster size, ie, school size), ρ is 0.02 (intracluster correlation coefficient). The resulting design effect was calculated as 3.98, yielding an adjusted sample size of 501 students per group. Allowing for an anticipated 10% dropout rate, the final required sample size is 557 students per group, totaling 1114 participants across all clusters. On the basis of the final required sample size of 557 students per group and an average cluster size of 150 students per school, the required number of clusters was calculated as 557/150=3.71 per group. Therefore, at least 4 schools per group, corresponding to a minimum of 8 clusters in total, are required.

The intervention group will receive 2 professionally administered FV applications. Applications will occur at baseline (month 0) and at 6 months, using Duraphat (Colgate-Palmolive Company) varnish, which contains 5% sodium fluoride by weight, equivalent to 22,600 parts per million fluoride ions [16,17]. The varnish will be applied to all erupted tooth surfaces by trained dental professionals under standard infection control procedures, including hand hygiene, appropriate personal protective equipment, and the use of single-use disposable materials to prevent cross-contamination, in accordance with Centers for Disease Control and Prevention guidelines for portable dental care [18]. A brief oral examination will be conducted prior to each session to confirm eligibility for varnish application. Prior to application, the teeth will be cleaned with sterile gauze and isolated with cotton rolls for moisture control [19]. The tooth surfaces will then be dried with gauze, followed by the application of 0.40 mL of 5% sodium fluoride varnish [20]. Concurrently, oral health education will be provided to parents and teachers of students. These educational sessions will be delivered during the school visits in which varnish applications occur. Content will include basic oral hygiene practices, the importance of fluoride in caries prevention, dietary advice, and strategies for supporting children with disabilities in maintaining oral health.

The control group will receive standard care, consisting of annual oral health examinations and oral health education. These educational components will be delivered during routine school visits using the same materials and format as in the intervention group, ensuring comparability of educational exposure between groups. However, no FV will be applied in control schools during the study period. The overview of the study is shown in Figure 2.

The primary outcome of this study is the prevalence of dental caries among students at 12 months following the intervention. Dental caries will be assessed through clinical oral examinations using the decayed, missing, and filled teeth index (DMFT) for permanent and primary dentition, respectively. These examinations will be conducted in accordance with the national standardized child oral health survey protocol used in China. Briefly, trained and calibrated dental professionals will perform tooth-level examinations using disposable dental mirrors and probes under natural or portable lighting. Dental status for both primary and permanent teeth, including caries experience and related conditions, will be recorded. Examinations will take place in a designated room with adequate lighting [21]. Children will be assessed while seated [22], and wheelchair users will remain in their own wheelchairs. Two familiar teachers or school support staff will attend to assist with communication and comfort [23]. A trained dentist will conduct the examination, and a trained nurse will record the number of decayed, missing due to caries, and filled teeth per child. The blank recording form is provided in Figure 3. To minimize measurement bias, examiners conducting the follow-up assessments will be blinded to the school allocation status.

Secondary outcomes include (1) oral hygiene status (eg, presence of plaque and gingivitis), assessed using gingival health indicators and plaque indices; (2) changes in oral health–related knowledge, attitudes, and practices (KAP) among students, parents, and teachers, measured using a structured questionnaire adapted from the Third National Oral Health Survey [24].

Baseline assessments will be conducted prior to intervention implementation, with follow-up occurring 12 months later. Oral examinations will be performed on-site in schools, with each child examined in a standardized manner. KAP questionnaires will be administered to parents and teachers at both baseline and the end of follow-up. All data will be collected using the Wenjuan Star platform (Shanghai Zhongyan Network Technology Co Ltd) or through paper-based questionnaires with double data entry, depending on the logistical feasibility at each study site. Data from paper questionnaires will be manually entered into the electronic system by trained students at the university. Details of the information collected are shown in Table 1. Monitors appointed by the trial sponsor will oversee trial implementation to ensure protocol compliance and data accuracy (Multimedia Appendix 1).

Data will be collected at baseline and at the 12-month follow-up according to prespecified study-specific procedures. Trained dental professionals will perform oral examinations. They will use the DMFT index [25]. Examiners also record periodontal status, including plaque index and gingival index, as well as tooth eruption and trauma [26]. At the same time, parents and teachers will complete structured KAP questionnaires. All paper records will be double-entered to reduce errors. Monitors will oversee the process to ensure protocol adherence and data accuracy.

All data will be entered into a centralized electronic data capture system with built-in logic checks to ensure completeness and internal consistency. Statistical analyses will be conducted using Stata (version 18.0; StataCorp LLC). Descriptive statistics will first be generated to summarize baseline characteristics of participants in both intervention and control groups, including means, SDs, proportions, and frequency distributions.

Comparative analyses between groups will be conducted on an intention-to-treat basis. Participants will be analyzed according to their randomized group, regardless of receipt of FV. For descriptive and unadjusted comparisons between groups, chi-square tests will be used for categorical outcomes (eg, caries prevalence). For continuous variables, independent-samples t tests will be used for normally distributed data, and nonparametric tests (eg, Mann-Whitney U test) will be applied for skewed distributions. Paired comparisons (eg, baseline vs 12-month follow-up) within groups will use paired t tests or Wilcoxon signed-rank tests as appropriate.

To evaluate the effectiveness of the intervention while accounting for potential confounders and cluster randomization in the primary analysis, mixed-effects logistic regression will be used for binary outcomes, such as caries presence, and mixed-effects linear regression for continuous outcomes, such as the number of decayed teeth [27]. Models will adjust for relevant covariates, including age, sex, socioeconomic status, and baseline oral health status. Multiple imputation with chained equations will be applied to handle missing covariate data. Cluster effects will be accounted for using robust SEs or multilevel modeling, as appropriate. Effect estimates will be presented as adjusted odds ratios or mean differences with 95% CIs. All hypothesis testing will be 2-sided, with a significance level set at P<.05. Sensitivity analyses, including subgroup analyses by economic region, will be conducted to assess the robustness of the findings.

This study has been approved by the institutional review board of Sun Yat-sen University (approval 2025‐065) and will be conducted in accordance with the Declaration of Helsinki and relevant national ethical guidelines. Prior to participation, detailed information about the study objectives, procedures, potential risks, and benefits will be provided to all participants and their legal guardians. Informed consent will be obtained from the guardians of participating students younger than 18 years. For students aged 18 years or older, informed consent will be obtained from either the participant or a legal guardian with participant assent [28,29] (Multimedia Appendix 1).

Although FV is considered safe and adverse events are uncommon, all potential adverse reactions will be monitored and recorded [30]. Any adverse reactions will be managed promptly, with medical referral and ethics reporting as required. Participation in the study is voluntary, and individuals may withdraw at any time without penalty. All personal data will be anonymized and stored securely in password-protected systems accessible only to authorized research personnel. Only deidentified data will be used for analysis and reporting to ensure confidentiality.

Biannual FV application, integrated with tailored oral health education for parents and teachers, is anticipated to be an effective intervention for caries control, significantly reducing the prevalence of dental caries among students in special education schools in Guangdong Province. We anticipate a significantly lower incidence of new caries and a higher rate of oral hygiene improvement—as measured by plaque and gingival indices—in the intervention group. Furthermore, the intervention is expected to significantly improve parental and teacher health literacy and oral health–related KAP scores. This study integrates professional clinical prevention with school-based education, aiming to generate critical evidence to inform national oral health strategies and policies for children with disabilities in China.

Although the efficacy of FV is well-documented in general pediatric populations, research specifically targeting children with disabilities in special education settings remains limited [6-9]. Previous studies in Asia have highlighted significant oral health inequities, noting that students with disabilities experience higher rates of dental caries than their peers without disabilities [1]. However, most prior work has been observational, focusing on the prevalence of oral diseases rather than evaluating systematic interventions within the school infrastructure [31-33].

This study uses a stratified cluster RCT design, enhancing internal validity and allowing for robust comparisons across different economic regions. The FV intervention is evidence-based and feasibly integrated into the school setting, facilitating scalable and routine implementation for high-risk populations. Standardized assessment tools and trained personnel are used for oral health examinations and data collection, ensuring measurement consistency and data quality.

Despite these strengths, several limitations should be considered. As the study is conducted within schools, findings may not be generalizable to children with disabilities who are not enrolled in special education institutions.

Future research may focus on the long-term sustainability of school-based fluoride programs beyond 12 months to assess whether caries prevention persists. Subsequent studies could also incorporate a cost-effectiveness analysis to help health authorities justify integrating FV into routine school health services.

Findings from this study will be disseminated through peer-reviewed scientific journals, presentations at national and international conferences, and briefings to policymakers and stakeholders in the health and education sectors. In addition, summary results will be shared with participating schools and local health authorities to inform the development of future oral health programs targeting children with disabilities.

By using a stratified cluster randomized design, the study will provide evidence on the effectiveness of integrating professional FV applications into the special education school environment. If the hypothesized reduction in caries and improvement in health literacy is confirmed, this model could serve as a blueprint for national health authorities to implement scalable, cost-effective oral health programs.