Automated phone call and text reminders for childhood immunisations (PRIMM): A randomised controlled trial in Nigeria

Background Sub-Saharan Africa has high under-5 mortality and low childhood immunisation rates. Vaccine-preventable diseases cause one-third of under-5 deaths. Text messaging reminders improve immunisation completion in urban but not rural settings in sub-Saharan Africa. Low adult literacy may account for this difference. The feasibility and impact of combined automated voice and text reminders on immunisation completion in rural sub-Saharan Africa is unknown. Methods We randomised parturient women at the Mother and Child Hospitals Ondo State, Nigeria, owning a mobile phone and planning for child immunisation at these study sites to receive automated call and text immunisation reminders or standard care. We assessed the completion of the third pentavalent vaccine (Penta-3) at 18 weeks of age, immunisation completion at 12 months and within 1 week of recommended dates. We assessed selected demographic characteristics associated with completing immunisations at 12 months using a generalised binomial linear model with log’ link function. Feasibility was assessed as proportion of reminders received. Results Each group had 300 motherbaby dyads with similar demographic characteristics. At 18 weeks, 257 (86%) and 244 (81%) (risk ratio (RR) 1.05, 95% CI 0.98 to 1.13; p=0.15) in the intervention and control groups received Penta-3 vaccine. At 12 months, 220 (74%) and 196 (66%) (RR 1.12, 95% CI 1.01 to 1.25; p=0.04) in the intervention and control groups received the measles vaccine. Infants in the intervention group were more likely to receive Penta-3 (84% vs 78%, RR 1.09, 95% CI 1.01 to 1.17; p=0.04), measles (73% vs 65%, RR 1.13, 95% CI 1.02 to 1.26; p=0.02) and all scheduled immunisations collectively (57% vs 47%, RR 1.13, 95% CI 1.02 to 1.26; p=0.01) within 1 week of the recommended date. No demographic character predicted immunisation completion. In the intervention group, 92% and 86% reported receiving a verification reminder and at least one reminder during the study period, respectively. Conclusion Paired automated call and text reminders significantly improved immunisation completion and timeliness. Trial registration number NCT02819895.

A two-arm parallel RCT was conducted at the Mother and Child Hospital Ondo Town (MCH-Ondo) and Akure (MCH-Akure), in Ondo State, Nigeria. The conduct, analysis and reporting of results are in accordance with the Consolidated Standards of Reporting Trials guidelines for reporting parallel group randomised trials.15 The Nigerian government provides routine childhood immunisation at no cost to recipients. Government-run immunisation clinics are locations where vaccines are routinely received. Dictated by the national programme on immunisation,16 the routine immunisation schedule in Ondo State, Nigeria is as follows: Immunisation clinic record-book audits were planned to assess vaccination uptake. However, the study was impacted by a hospital workers’ strike lasting 6 weeks (2 February to 15 March 2017). The strike interrupted enrolment, immunisation receipt and monitoring. During this period, parents sought other government and private clinics for immunisations. We therefore amended our study protocol to include phone audits for reporting of immunisation uptake between weeks 18 and 30 of each participant’s study enrolment period. This was to limit misclassification of the immunisation endpoint. We incorporated the phone call immunisation audit into the planned mid-study survey. The applicable ethical review bodies approved the amendment. Parturient women and their healthy newborn infants delivered at MCH-Ondo and Akure were eligible for enrolment. We included mothers of healthy newborn babies, who owned a mobile phone and planned to attend the MCH immunisation clinics. We excluded mothers of ill newborns, multiple births and those without mobile phones. The MCHs are state-run facilities. They provide free healthcare services to pregnant women and children under age 5, with most patients being middle-income and low-income families. Each hospital runs its own immunisation clinic. Ondo State is in the southwest region of Nigeria. The main local language is Yoruba. The projected 2016 population size from the 2006 national census for Ondo Town and Akure are 389 900 and 486 300, respectively.17 The primary occupations of citizens include farming, artisanship, trading and public service.17 We developed a customised Windows software application (app) designed to send automated voice call text and email immunisation reminders. We integrated a secure cloud communications platform, called Twilio, into the app. Messaging and voice were sent by Twilio through the app. Date of birth of the newborn and the phone number of the mother and father, when provided, were inputed into the app. The immunisation reminders were autocalculated from date of birth of the child and tailored to the local immunisation schedule. At enrolment, the registered phone number(s) received a verification message. Thereafter, reminders were sent 2 days and the day before the scheduled date of the Penta-1, 2, 3 and measles immunisations at 08:00. Eight sets of reminders were sent to each participant. The delivery of text and call occurred at the same time. Voicemail service was not available during the study period. The automated text message reminder was in English. The text reminder read, ‘Reminder from MCH–Your baby’s next immunisation visit is in 2 days (or 1 day as appropriate). Immunisation protects your child against killer diseases. Please bring your baby for this visit’. The automated call reminder was in English and Yoruba. The duration of the call was 50 s, had a 5 s delay before starting and expressed the same message as the text. It cost US$0.0075 to send a text and US$0.015/min for an automated call. There was no cost to the recipient. Whether study participants received or read the text message and whether participants listened to audio messages in its entirety could not accurately be determined from our telecommunications platform. A research assistant at each site assessed mothers daily in the postpartum ward for eligibility. We systematically recorded the number of screened women and the reason for exclusion; however, due to a clerical error at MCH-Ondo, the exact numbers and reasons are unavailable. In developing the study protocol, we took into consideration that the shortest interval between the pentavalent vaccines is 3 weeks. In Nigeria, the immunisation schedule allows for only 4 weeks between Penta-1 and 2, and between Penta-2 and 3.18 We anticipated a potential stacking of reminders, and immunisation ineligibility, if there was any delay in receiving a scheduled immunisation greater than 1 week. Hence, a priori, we determined the reminders for Penta-2 and 3 would be recalculated from the date the Penta-1 and 2 were administered, respectively. For those who did not receive either Penta-1 and or 2, the Penta-2 and 3 reminders were sent 2 weeks after the Penta-1 and 2 were past due, respectively. We performed daily audits of the immunisation clinic record book. When vaccines were received later than expected, the vaccine receipt date was used to calculate the next scheduled vaccine accordingly. A child-health immunisation card, which listed the ages when a child was to receive his/her immunisation, comprised standard care. The intervention group received the automated text and call reminder plus standard care, while the control group received only standard care. We obtained data for the primary outcome from immunisation clinic record books maintained at immunisation clinics and during the mid-study phone survey of all participants. Study research assistants called each study participant on the telephone and obtained verbal reports─name and date─of when Penta-1, 2 and 3 were received. We assessed the receipt of measles vaccine solely from the immunisation clinic record book. This was because the health workers’ strike did not affect the receipt or monitoring of the measles immunisation. We did not physically audit the child-health immunisation card given to parents and caregivers. The primary outcome was the proportion of infants who received the Penta-1, 2 and 3 immunisations (henceforth referred to as Penta-3) at 18 weeks of age. The administration of BCG vaccination occurs at hospital discharge. Our intervention did not influence BCG receipt, and so it was not included in our primary outcome. We defined the secondary outcomes as completing Penta-3 and the measles immunisation by 12 months of age and receiving each within 1 week of the recommended time. We assessed feasibility by the proportion of participants who received the verification text and call at enrolment, as well as those who reported receiving the reminders during the mid-study survey. Additionally, using a socioecological framework, we designed and administered a pre-study survey to assess sociodemographic characteristics of the mothers. We categorised the survey questions into maternal demographics, knowledge about and attitude towards immunisations, mothers’ health and health-seeking behaviour, household demographic construct and access to health facility and health information related to immunisation. The mid-study survey was to assess acceptability of the intervention, perception of phone reminders by both groups and perceived barriers to completing immunisations. Mother–infant dyad assignments to study groups in a 1:1 ratio was by a permuted randomisation scheme,19 using balanced random blocks of 6, 8 or 10. We stratified the randomisation by study site to account for centre population differences. Randomisation was done in May 2016 at The Children’s Hospital of Philadelphia. Allocation assignments were stored in sealed opaque envelopes and mailed via courier to the local study principal investigators. Only after obtaining written informed consent did the local study teams know the allocation assignment. Neither study participants nor research team were blinded. However, the immunisation clinic staff─those who administered and recorded immunisation─were blinded to study group allocations. Based on audits of the 2015 MCH-Ondo immunisation records and statewide reports, the baseline Penta-3 completion rate estimate was 75%. To account for a 10% loss to follow-up, we needed 300 mother–infant dyads in each study arm to have a statistical power of 80% and an alpha level of 0.05, to detect a 10% difference in the primary outcome. We deemed this 10% difference to be of public health importance. With the protocol amendment, we defined two study populations for the primary outcome analysis. First, a modified intention-to-treat (mITT) population─defined as all randomised subjects regardless of where immunisation was received or audited—immunisation record books or phone calls. The second was the per-protocol (PP) population─defined as all subjects who received immunisations only at MCH-Ondo or Akure and had immunisation receipt audited solely from the immunisation clinic record books. We compared demographic characteristics and post-study survey variables between study groups using standard descriptive statistics. We used two-sample t-test or Wilcoxon rank-sum test for continuous variables and χ2 test or Fisher’s exact test for categorical variables. Risk ratios and risk difference were calculated for the primary and secondary outcomes. In a post hoc analysis, we used a generalised linear model for binomial distributions with ‘log’ link function to examine the association of selected demographic characteristics by study group on immunisation completion at 12 months. The selected variables were based on demographic factors reported in the literature to influence immunisation completion.5 10 20–22 We tested interaction effects of the demographic factors with the study group and report the p values for the interaction effects. Results are expressed as risk ratio along with their corresponding 95% CIs. Data were analysed using Stata V.15.1 (StataCorp, College Station, Texas, USA) with a two-sided significance level of 0.05.

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