Study setting:
The city of Boa Vista has a population of approximately 330,000 people, with, 22,377 families (~30%) currently receiving or enrolled in social cash transfers under the bolsa familia program, very similar to the national average (35% of the population) [27]. According to the Municipality health secretariat, infant mortality rate is estimated at 14.2 per 1000 live births, with 21% of births by teenage mothers and 11% of infants born preterm [28].
Eligibility criteria:
Study eligibility is restricted both spatially and at the individual level. As mentioned in the Study Design section, the scale-up targets only vulnerable neighborhoods. Boa Vista social services classify all neighborhoods based on literacy rates, average per capita income (less than ¼ of the minimum wage), access to water, sanitation, sewage systems and electricity into A (low vulnerability), B (medium vulnerability) and C (high vulnerability) areas. Out of the 55 neighborhoods in Boa Vista, 12 were classified as “high socioeconomic status (A), 14 were classified as “low vulnerability” (B) and 29 were classified as “high vulnerability” (C). The study was restricted to the 43 B and C areas.[1]
Within all target areas, all pregnant women as well as women with children under the age of one are eligible for the program as long as they are either poor, were under the age of 20 at the time of conception or were ever exposed to domestic or sexual violence.
Interventions:
Home visit arm (Arm 1):
The intervention will be delivered during fortnightly home visits with the presence of the child and at least one of the main caregivers (the program focusses on the mother, but ideally with the father participation or any other family member that routinely spends time with the child). The home visiting curriculum is divided in 3 main modules: 1) pregnancy module: this module is designed to make mothers aware of pregnancy danger signs, to encourage adherence to antenatal care (attendance, performing exams and supplementation), to improve bonding and positive parental practices and to prepare women for breastfeeding. 2) Neonatal module: comprises 3 home visits during the baby’s first month of life. One visit during the first week, a second visit at 15 days and the third visit at 28 days. The primary focus of these visits is babies’ health, breastfeeding and bonding. 3) child module for ages 2-36 months. Each home visit has 3 or 4 play activities to address child development domains (gross motor, fine motor, language, cognitive development and social emotional development). A recycled materials toy kit is used to support these activities. Visits take in average 45 minutes; after demonstrating and practicing each activity with the caregiver, the visitor leaves the toys, and mother/caregiver is encouraged to play and interact with the child in the two-week interval between the visits. Activities are age-appropriate, and toys and learning materials are exchanged for a new set at each visit. Home visits will be conducted by newly hired and trained child development agents, who will be tasked to complete 60 home visits per month (3 visits per workday), supporting 30 families.
Group-meeting arm (Arm 2):
Group meetings are designed to deliver essentially the same content. Meetings are held fortnightly at the CRAS center (Social Services Centers) for groups of 8 mothers and their children, other members of the family can participate as well. Groups are formed with participants at a similar stage of gestation or with children of similar age. Group composition remains fixed to increase bonding over time. The only difference between the center and the home-based curriculums is the number of activities per session: due to the larger number of participants, the number of activities is reduced to 2 at centers. The neonatal module is also reduced to 1 or 2 sessions, since we do not expect mothers to attend the sessions during the first 2 weeks of babies’ life. Group moderators will be hired by the project and will be tasked to schedule 3 age-groups specific 1 hour and 30 min sessions each day.
Program teams will be based at the 7 regional social service units (CRAS) and will deliver the intervention according to the services coverage area. Group meetings will be held at the centers, where a meeting room will be fully dedicated to the project and are more easily accessed by mothers, since they are distributed within the more vulnerable areas.
Attendance to the sessions, dropouts and refusals will be registered at the intervention logs and monitored by the team in a monthly basis. In order to improve adherence, if a participant skips 3 consecutive sessions, she will be contacted by the delivery team supervisor to understand reasons and eventual problems that need to be addressed to continue participation. The dropout log, registries the motives for discontinuity, and depending on that, the supervisor can also contact the participant to revert dropout.
Control group (Arm 3):
Pregnant women living in the control group allocated neighborhoods will receive the regular public services provided by the municipality. In terms of Health care, they will receive primary, secondary and tertiary care through the primary care units and hospitals run by the municipality or state secretariat. They will also have access to the regular social services provided by the Social Services Units and to other social (and cash transfer) programs such as the Bolsa Família.
Modification of Interventions or Protocols
After the trials started, there will be no special criteria for discontinuing or modifying allocated interventions. The research group will monitor in a monthly basis protocol adherence aspects such as group allocation, participation, logs and other registry instruments and will participate in the weekly delivery team meetings and supervise home visits and group-meetings.
No protocol amendments are expected during the trial but the PI will notify funders, the municipality and the IRB if any changes should be needed. Any deviations from the Protocol will be documented using a breach report form and the protocol will be updated in the clinical trial registry.
Adherence
Program rollout will be closely monitored by the steering committee. Before the trial launch, the municipality agreed not to deliver similar concomitant intervention for this population in the selected neighborhoods. To ensure this will not happen in practice, the research group will collect information on other social programs participation.
Concomitant and Post-trial Care
Implementing the two ECD interventions will not require alteration to usual care pathways (including use of any medication). Standard medical and child support care will be available to all study arms throughout the trial. There is no anticipated harm and compensation for trial participation during or after the trial. All participants will continue to have regular access to public health and social services once the trial is over. The continuity of the intervention after the trial is dependent on the mayor discretion.
Outcomes:
The primary study outcome is child development at age 2 as assessed by the PRIDI scale. The secondary study outcome is child survival, which will be assessed using data from the municipality’s vital registration system (SIM and SINASC). Maternal depression will be assessed using the Center for Epidemiologic Studies Depression Scale (CES-D Scale).
Intention to treat analysis will be used to compare outcomes across the 3 study arms.
Additional per-protocol analysis will be conducted using data on program compliance. Our primary measure of compliance in the home visiting arm will be the number of home visits completed. Our primary compliance measure in the center-based groups will be the number of sessions attended by the mother.
Randomization
Randomization of program rollout timing was based on a simple random number draw in Stata. The number of treated areas in phases 1 and 2 were determined based on logistical feasibility and an initial agreement between the municipality and the project team: in phase one, 9 areas were chosen for home visits and 2 for center-based programs. In phases 2 and 3, program reach was gradually increased to reach all communities as outlined in the Study Design section above. In phase I, 11 neighborhoods will receive the intervention; in phase II, 27; in phase III, all B and C neighborhoods will receive interventions. Figure 3 summarizes the neighborhood selection process and shows the random allocation of interventions by phase. Figure 4 shows the spatial location of areas chosen for each intervention phase.
Recruitment
Recruitment for this project will be implemented in close collaboration with the Municipality Secretariat for Social Wellbeing and Health (SSWH). The SSWH identifies eligible pregnant women each month, and links them to the project team. Each woman is then visited by study staff and, conditional on their consent, completes a baseline interview. According to the municipality of Boa Vista, there are approximately 600 new pregnancies per month. The baseline forms are then used to establish eligibility for the program. As stated above, the following three (non-mutually exclusive) groups of women are eligible for the program:
- Household classified as poor
- pregnant women under age 20 (teenage pregnancies)
- women with previous exposure to partner violence
In the first few years of the program, a small sample of women with children under age 1 will also be enrolled. This sample will be used to assess the relative impact of reduced exposure to the interventions.
In order to achieve enrollment to reach the sample size, the research group hired and trained a team of interviewers that will visit the eligible participants from the municipality list, but also actively search for other potential participants in the field. The research team will use the municipality official birth records in a monthly basis to monitor eventual not enrolled new children born in the catchment areas and enroll them afterwards.
Given that we will have 12,000 participating households in the intervention, we do not foresee any difficulties reaching the 3,000 sample size target for endline
Blinding: Given the nature of the intervention, blinding of participants is not possible. Endline interviewers will be blind to group assignment.
Monitoring and Potential Harm
Given that the intervention does not present a risk for the population and that the municipality has committed to delivering interventions following the established timeline, there are no formal stopping rules for this trial. We also do not foresee any interim analysis for such purposes. However, even if not related to the intervention the home visitor or group facilitator presents or is informed of any adverse event such as domestic violence, or health risk, it will be reported to the supervisor and to the Social Service Unit manager, and relevant regulatory bodies as required indicating expectedness, serious-ness, severity, and causality.
Sample size and power calculations
Based on the estimated number of births in the targeted B and C areas, we anticipate completing approximately 12,000 baselines (screening interviews) over the project period. Out of these mother-child dyads, we will randomly select 3000 for the endline assessment. We assume an average causal effect of 0.5SD on compliant mothers. With an anticipated average compliance rate of 50%, the study is powered to detect an intent-to-treat effect of 0.25SD with power 0.9 between each of the two intervention arms and the control arm, assuming an average sample of 120 households in each of the 11 neighborhoods treated in Phase 1, and an average sample of 60 households in each of the 28 control neighborhoods, assuming an intra-class correlation of 0.02..
In order to assess spillovers within households, we will also assess all older siblings under age 4 in households selected for endline. Based on the high fertility rates observed at baseline, we anticipate a sample of 750 older siblings. Assuming a uniform distribution of siblings across clusters, the study is powered to detect a 0.3SD change in PRIDI score with power 0.8.
In order to assess domain-specific changes in children’s development, we will also invite 80 mothers from each arm for a detailed assessment using the Bayley’s Scales for Infant and Toddler development. For these assessments, we will randomly select moms from the control group as well as compliant mothers from the two intervention arms.
Timeline
Baseline survey collection started in December 1 2017 and will be finished by July 2020. Home visits team was trained in November 2017 and visits were launched shortly after initiation of baseline in Phase 1 home visiting areas; the first births within this group occurred in February 2018. Due to logistical challenges, center-based programs were started later; the two areas randomly selected for Phase 1 of the project were formally launched in July 2018. Phase II (both for home visits and center-based programs) was started in July 2019, with 10 neighborhoods added to home visiting programs, and 8 added to center-based programs.
Endline surveys are scheduled to start in April 2020 and will target children at age 2. With the targeted sample size of 3000 households we anticipate to complete endline by July 2021. BSID-3 assessments will start in July 2020 and should be completed within six months.
Data management:
Baseline and endline data will be collected in electronic format on tablets and storied on a secure server. The project leader will be responsible for the anonymization of the data system. A unique identifier will be used in the data system to preserve participant’s privacy and confidentiality.
Statistical methods:
For statistical analysis, standard regression models will be used for the continuous PRIDI outcome. Logistic regression models will be used for the secondary mortality outcome. All analysis will be conducted using the Stata 15 statistical software package. Primary analysis will be intent-to-treat. To assess the impact of partial compliance, we will also estimate average treatment effects on the treated (per-protocol analysis).
Ethical clearance:
The study was approved by the Researcher’s institution IRB under protocol number CAAE:73722917.4.0000.0076 in August 2017.
Consenting:
Each participant signs the consent form at enrollment, during the baseline interview visit. Should the participant be a minor, the consent form is signed by a legal representative. On the consent form, participants will be asked if they agree to use of their data should they choose to withdraw from the trial. Participants will also be asked for permission for the research team to share relevant data with people from the Universities taking part in the research or from regulatory authorities, where relevant. This trial does not involve collecting biological specimens for storage.
The consent form is signed in two copies, so that the participants can keep a copy of the signed consent form. PI’s, the Social services responsible and IRB’s contact information are provided in the consent form, so that participants can reach out in case of questions or other issues. Copies of the consent form are available from the corresponding author on request.
Trial Status:
As of November 2019, trial enrollment is open and is scheduled to continue until July 2020. The present protocol is in its first version, since November 2017.
[1] Three of these areas were chosen for municipality programs and excluded from the main study.