Trial design and settings
The Mobile Link intervention study is a multisite 60-week randomized controlled trial (RCT). The trial was conducted in two sites in Phnom Penh and one site each in Banteay Meanchey, Battambang, and Siem Reap. These provinces were selected because of substantial populations of FEWs and high HIV burdens.
The intervention’s participant inclusion criteria included: (1) working at an entertainment venue in the study sites; (2) being currently sexually active, defined as having engaged in oral, vaginal, or anal sex in the past three months; (3) owning a mobile phone; (4) knowing how to retrieve VM or retrieve and read SMS; (5) self-identifying as a FEW; (6) willing to receive two SMS/VM per week for one year; (7) providing written informed consent; and (8) agreeing to a follow-up visit after six months and 12 months.
Field workers developed a list of more than 4000 FEWs from the five study sites. FEWs in the list were categorized by site and age group (18–24 and 25–30 years old). At each site, 60 FEWs were randomly selected (30 in the age group of 18–24 and 30 in the age group of 25–30) for each arm (300 FEWs in the intervention and 300 FEWs in the control arm) for a total of 600 study participants.
All participants were recruited in-person at the five study sites by trained Mobile Link lay community health workers. Community health workers provided verbal information to FEWs regarding the Mobile Link’s details because of low literacy rates in this population. Eligible FEWs signed the informed consent form and provided community health workers with mobile numbers for all of their subscriber identification module (SIM) cards and indicated which SIM they used most often. Recruited FEWs were assigned a unique identification number to protect their privacy and blind the researchers from their treatment arm assignment.
At the midline, the data collection team recruited additional study participants to replace those who were lost to follow-up by randomly selecting FEWs from the same site and age group on the master list, excluding those that had ever been selected. These replacement participants had the opportunity to participate in the second 30 weeks of the intervention period. We considered participants having at least two survey assessments to be active participants in the study.
Patient and public involvement
This clinical trial was developed after months of iterative qualitative data collection with FEWs, including 27 focus group discussions, nine in-depth interviews, and two validation workshops. During this period, participants gave researchers guidance and feedback on the design and delivery of the intervention and recruitment and data collection procedures. Dissemination activities involve extensive focus group discussions, in-depth interviews, and a final validation workshop.
The Mobile Link intervention was informed by both behavior change theories and extensive formative research. The intervention provided FEWs with information, resources, and reminders. By utilizing an SMS/VM platform, these services were provided in a convenient, accessible, inexpensive, and confidential manner. Therefore, we theorized that this delivery mechanism would improve FEWs’ knowledge of existing resources, risks, risk behaviors, and positive attitudes related to these topics. Increasing knowledge and positive attitudes will contribute to skill acquisition and positive behavior change.
We conducted a series of formative research activities using participatory methods to create appropriate and relevant health-related messages for FEWs and inform the intervention’s development. The formative research process occurred over six months. We collected data through focus group discussions (FGDs), in-depth interviews (IDIs), and key informant interviews (KIIs) with the venue- and non-venue-based FEWs in addition to outreach workers and field staff that routinely work with this population . Findings from the formative research revealed that FEWs were generally knowledgeable about HIV and STI prevention and transmission. However, they faced many structural barriers to optimal health, such as pressure to drink alcohol at work and complicated dynamics of negotiating condom use with clients in a criminalized environment [25, 26]. Furthermore, we found that many FEWs faced barriers to accessing medical care and services due to stigma, discrimination, and mistreatment from healthcare workers.
Development of the message-based intervention was conducted with the support of local partners, InSTEDD iLab and the Women’s Media Center (WMC). InSTEDD developed the mobile platform for interactive message delivery and data management using an open-source software program. The WMC helped translate messages into Khmer and tailor the contents to be specific, relevant, and engaging, given the cultural context. Example messages included can be found in a previously published paper .
After development, the intervention underwent a four-week pilot in which 50 FEWs from each study site were randomly selected. The purpose of the pilot was to test whether the platform functioned well with the intervention design and whether the intervention was feasible and acceptable for the participants.
The central components of the Mobile Link intervention were the SMS and VM messages, containing health information, and referral linkage information to health services and resources. From the formative research process, 180 messages were designed covering ten health themes identified as the most important by participants. The health themes covered the following topics: cervical cancer, contraception, general health information, HIV and STI transmission and prevention, miscarriage, pregnancy, alcohol use at work, pregnancy termination, hygiene and vaginal health, and GBV. A message was delivered twice a week for ten weeks, and the message from each topic area was repeated every ten weeks for 60 weeks. The health messages were framed using rights-based and health promotion frameworks. Participants could choose to receive the messages in an SMS or VM form that worked with simple and smartphone devices. Those who chose the SMS message option could further personalize their choice by selecting Khmer characters or Romanized Khmer. Each health topic message was followed by a message providing FEWs with the option to be linked to an outreach worker. Participants who selected this option were called by the Mobile Link’s staff, who would provide individualized information via telephone or face-to-face and, if needed, would escort the participant to services.
The control for this study received the existing standard care. Standard care included face-to-face counseling, free HIV and STI testing and condoms, and clinic phone numbers and hotline phone numbers with a toll-free help-line for clients staffed by trained counselors. The group did not receive the health-related SMS/VM component. However, they will receive a “check-in” SMS or VM between baseline and midline and another between midline and endline to stay in touch with the participants and remind them of the interview appointments.
Outcomes and measures
The primary outcome measures of the Mobile Link intervention were: (1) HIV testing, (2) STI testing when experiencing symptoms, (3) contraceptive use, (4) always use condoms with non-paying partners, and (5) always use condoms with paying partners. The secondary outcome measures were: (1) contact with outreach workers, (2) utilization of escorted referrals, (3) forced drinking at work, and (4) responses to GBV and GBV acceptance.
The primary and secondary outcomes were tracked and measured using self-reported data from the baseline, midline, and endline surveys. The survey questionnaires contained items on demographics and background history; entertainment work; sexual behaviors; condom use self-efficacy; HIV risk perception, testing, and treatment; STI testing and treatment; contraception use and pregnancy; GBV and inequity; substance abuse; psychological distress; linkage to health services; and exposure to the Mobile Link intervention. The questionnaires contained approximately 100 questions, which were either dichotomous (e.g., yes/no), categorical (e.g., type of contraception method used), ordinal (e.g., always, frequently, sometimes, and never), or a ratio (e.g., number of years working in entertainment venues). The questionnaires were adapted from validated questionnaires used in our previous research in FEWs in Cambodia. The questionnaires were created in English, translated to Khmer, and back-translated to English. The Khmer questionnaires were validated via a pilot test of 15 FEWs with similar characteristics to the intervention participants, who were later excluded from the main surveys.
The data collection process involved a baseline, midline, and endline questionnaire survey and weekly monitoring data. The questionnaires were administered in-person in Khmer by the Mobile Link’s female field researchers using the open-source Kobo Toolbox software installed on Android-operating tablets. Before data collection, the field researchers underwent two-day training in which the questionnaire was also pretested. Field staff connected FEWs to field researchers by making appointments with FEWs, following up the appointments, and guiding FEWs to predetermined interview locations. We conducted the baseline survey before the start of the intervention (March 2018), the midline survey at six months after baseline (November 2018), and the endline survey at 12 months after baseline (June 2019). The questionnaires took approximately 25 to 30 minutes to complete, and the field researchers were blind to the FEWs treatment arm assignment to reduce the possibility of bias.
The Mobile Link intervention engaged community and public health stakeholders to ensure that the study incorporates best practices and strong ethical standards. Due to the sensitive nature of HIV, SRH, and GBV topics presented in the surveys and questionnaires, additional steps were taken to ensure participants’ safety and well-being. First, all data collectors received training related to asking sensitive questions. Second, upon obtaining informed consent, community health workers disclosed information, making clear the sensitive topics discussed in the data collection process. Third, participants were offered escorted referrals to counseling services and provided with services upon request. Participants could be connected to services in the event of an adverse outcome through the SMS/VM platform. Also, participants could leave the study at any time. Furthermore, participants’ identities were kept confidential and stored securely in password-protected files. Coded identifiers were given to participants after obtaining informed consent. No participants’ personal identifiers were used in analyses or report writing. Participants received $5 in compensation and transportation reimbursement for their participation.
STATA/SE 15.1 (College Station, TX, USA) was used for statistical analyses. We tabulated participants’ baseline characteristics and distributions of primary and secondary outcome variables for intervention versus control arms for the analytic sample – participants with at least two observations – using frequencies and proportions for categorical variables and means and standard deviations (SDs) for continuous variables. These characteristics were compared by group using tests of association, including Pearson’s Chi-squared tests of homogeneity for categorical variables and paired Student’s t-tests for continuous variables to ensure the balance between the study arms. We conducted both crude and cluster-adjusted pooled tests of association to account for clustering within workplace venues. Participant characteristics were then compared for the analytic sample (n = 388) versus non-analytic sample (n = 733) to assess significant differences within and between groups for those retained in the study per protocol for at least two survey assessments (i.e., analytic sample) versus those lost to follow up after the baseline assessment (i.e., non-analytic sample).
Intervention effects were assessed using multilevel mixed-effects logistic regression to model all binary outcomes accounting for within-subject correlation from taking repeated measures on the same participants over time (two-level models with observations nested within individuals). Clustered standard errors were computed to account for the similarity of characteristics and behaviors among participants in the same venues. Separate models were conducted for each primary and secondary outcome. Model fit was assessed for each outcome using the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC).
Predictors in each simple unadjusted two-level mixed-effects logistic regression model included: group, time, and group by time interaction terms. Intervention effects for each outcome were determined by group by time interaction terms at endline with a significant p-value < 0·05. Odds ratios (ORs) and 95% confidence intervals (CIs) for intervention effects at endline are displayed in Tables 2 and 3 (group by time interactions at time 3). Significant interactions indicating intervention effects were graphed using the marginsplot command (Figs. 1–3). Midline effects (significant group by time interactions at time 2) are displayed in the figures but not in the tables. For the fully adjusted primary and secondary outcome models, the following covariates were included to control for alternative explanations: entertainment job venue type, province, cohabitation, age, and education. For primary outcomes, contact with outreach workers in the last six months was also included as a covariate to assess the impact of linkage support on HIV and STI testing, contraceptive use, and condom use.
As a sensitivity analysis, we used intention-to-treat (ITT) principles for modeling primary and secondary outcomes with all participants (n = 1121), according to the arm to which they were assigned and then compared to the results for each outcome from the per-protocol modeling with the analytic sample. Per-protocol analyses were undertaken to assess the intervention’s impact among those who actively participated in the study. Participants lost to follow-up after baseline, resulting in missing outcome data at six months, were considered non-users. ITT and per-protocol results were consistent for all outcomes regarding the direction, strength, and significance of associations. As such, only the per-protocol results are presented in the tables for ease of interpretation.
There are several protocol deviations to note. The original protocol called for a 12-month (52 week) trial. However, due to high dropout rates at the midterm, we extended the trial to 60 weeks to recruit and enroll more participants who would have the chance to be exposed to the intervention for at least 30 weeks.
We did not anticipate the level of loss to follow-up that occurred and, therefore, did not have a plan in place for replacement recruitment in our original protocol. We decided to recruit replacement participants at the midline by randomly selecting FEWs from our master list from the same venue and age group. In our analyses, we defined exposure as having had at least 30 weeks of exposure to the intervention.
Another deviation occurred in our group assignment plan. Initially, we planned to randomize at the entertainment venue level to conduct a cluster RCT. Before the implementation, we changed our trial design to randomize at the individual level due to the high level of movement of FEWs between venues. As a result, we modeled intervention effects using the individual rather than the venue as the analysis unit. We computed clustered standard errors based on the venue rather than including the venue as a level in the mixed-effects outcome models. Finally, we included the venue type (e.g., karaoke bar, beer garden, etc.) as a covariate in all our models.
In our protocol, we planned to send out weekly survey questions to intervention participants on various health topics. During intervention development, we heard from pilot participants that they felt reluctant to give that type of information through the phone. We were also concerned about message fatigue, privacy, and literacy and decided to omit that part of the intervention.
Finally, in our protocol, we stated that we would present an ITT analysis. Because the ITT and per-protocol findings were the same, we decided to present the per-protocol analysis for ease of interpretation.