JRPemHabaARRAAKVEIREU1iAtgopiitidcnh0ARTICLE IN PRESSG ModelVAC-16417; No. of Pages 19Vaccine xxx (2015) xxx–xxxContents lists available at ScienceDirectVaccinej our na l ho me page: www.elsev ier .com/ locate /vacc ineeviewarental reminder, recall and educational interventions to improvearly childhood immunisation uptake: A systematic review andeta-analysisannah Harveya,∗, Nadja Reisslanda, James MasonbDepartment of Psychology, Durham University, Durham DH1 3LE, UKDurham University School of Medicine, Pharmacy and Health, Wolfson Research Institute, Stockton-On-Tees TS17 6BH, UK r t i c l e i n f orticle history:eceived 16 January 2015eceived in revised form 21 April 2015ccepted 23 April 2015vailable online xxxeywords:accinationarly childhoodnterventionecall and remindera b s t r a c tVaccination is one of the most effective ways of reducing childhood mortality. Despite global uptakeof childhood vaccinations increasing, rates remain sub-optimal, meaning that vaccine-preventable dis-eases still pose a public health risk. A range of interventions to promote vaccine uptake have beendeveloped, although this range has not specifically been reviewed in early childhood. We conducteda systematic review and meta-analysis of parental interventions to improve early childhood (0–5 years)vaccine uptake. Twenty-eight controlled studies contributed to six separate meta-analyses evaluatingaspects of parental reminders and education. All interventions were to some extent effective, althoughfindings were generally heterogeneous and random effects models were estimated.Receiving both postal and telephone reminders was the most effective reminder-based intervention(RD = 0.1132; 95% CI = 0.033–0.193). Sub-group analyses suggested that educational interventions wereducationptakemore effective in low- and middle-income countries (RD = 0.13; 95% CI = 0.05–0.22) and when conductedthrough discussion (RD = 0.12; 95% CI = 0.02–0.21). Current evidence most supports the use of postalreminders as part of the standard management of childhood immunisations. Parents at high risk of non-compliance may benefit from recall strategies and/or discussion-based forums, however further researchis needed to assess the appropriateness of these strategies.. IntroductionThe reduction in global mortality associated with vaccinationss second only to the introduction of safe drinking water [1].ccording to the World Health Organisation, childhood vaccina-ions prevent an estimated 2–3 million deaths per year. Yet despitelobal increases in childhood vaccine uptake, rates remain sub-ptimal (<95%), with vaccine-preventable diseases still posing aublic health risk [2]. Neither is this risk limited to low- and middle-ncome countries (LMICs). Factors such as poor access to healthcare,ndigenous or ethnic status, a large family size and low educa-ional achievement are associated with pockets of low coveragen high-income countries (HICs) [3].Please cite this article in press as: Harvey H, et al. Parental reminder,immunisation uptake: A systematic review and meta-analysis. VaccinMaintaining reductions in mortality from vaccine-preventableisease relies upon continued immunisation uptake that, duringhildhood, is reliant on parental decision-making and subsequent∗ Corresponding author. Tel.: +44 0191 334 3251.E-mail addresses: hannah.harvey@durham.ac.uk (H. Harvey),.n.reissland@durham.ac.uk (N. Reissland), j.m.mason@durham.ac.uk (J. Mason).ttp://dx.doi.org/10.1016/j.vaccine.2015.04.085264-410X/© 2015 Published by Elsevier Ltd.© 2015 Published by Elsevier Ltd.attendance at vaccine clinics [4]. However, several factors may actas barriers to childhood immunisation. Factors include parentalconcerns about vaccine safety, a lack of knowledge about therecommended schedule, pain caused by the injections, distrustof the medical community and difficulty accessing clinics [5].Therefore, it is important to understand the effectiveness ofinterventions implemented by primary care settings that aredesigned to improve childhood immunisation. Interventions toincrease childhood immunisation have been targeted at a varietyof groups, including healthcare providers, healthcare practicesand parents [6]. This review will focus on the effectiveness ofinterventions targeted at parents. Many strategies have beentrialled, including financial incentives [7] and home vaccination[8]. However, as the majority of trials have addressed (a) the lackof schedule awareness using parental reminder systems and/or(b) knowledge about the safety and efficacy of vaccines througheducational leaflets or discussion-groups, these interventions will recall and educational interventions to improve early childhoode (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085be the primary focus of this review. Systems designed to remindparents that their child was due (reminder) or overdue (recall)their immunisations have been linked to a 1.5 times increasein uptake [9]. The effects of parental education are less clear, ING ModelJ2 ccine wustctIiiptdi22EF(dfiTysoip2rTONaJt2RE0ARTICLEVAC-16417; No. of Pages 19 H. Harvey et al. / Vaith evidence presented both for [10,11] and against [3] theirtility.Previous reviews have focussed on the efficacy of interventiontrategies in isolation and not all have made specific recommenda-ions regarding childhood immunisations. Today, primary healthare services are under increasing pressure to meet immunisa-ion expectations at both an organisational and patient level [12].n order to facilitate physician judgements about interventions toncrease childhood immunisation, and to increase the efficacy ofntervention implementation and policy updates, a review com-aring the effectiveness of multiple interventions to be compared isimely. Therefore, a systematic review and meta-analysis was con-ucted to evaluate available evidence on parental interventions tomprove childhood (birth to 5 years) vaccine uptake.. Material and methods.1. Literature searchA systematic literature search of five databases (MEDLINE,MBASE, EMBAR, CINAHL and PsychINFO) was conducted inebruary 2014 using the OVID and EBSCOhost search platformswith adaptation of terms for EBSCOhost). Search terms were pre-efined to allow a comprehensive search strategy that included textelds within records and Medical Subject Headings (MeSH terms).erms related to immunisation, immunisation uptake, infants andoung children and intervention study design. The OVID searchtrategy is reported in Table 1. This search was conducted as partf a wider review of barriers and facilitators of childhood immun-sation and so included both qualitative and quantitative data. Theresent review refers only to quantitative intervention studies.Please cite this article in press as: Harvey H, et al. Parental reminder,immunisation uptake: A systematic review and meta-analysis. Vaccin.2. Study selectionDatabase search results were combined and duplicates wereemoved. Studies were screened for eligibility by the primaryable 1VID search strategy.Search no. Search terms (number of records found)1 Vaccination/or vaccin*.mp. (504,709)2 Vaccines, Combined (Roberts et al.) (15,179)3 Immunisation, Secondary/or ImmunisationSchedule/or immuniz*.mp. or immunis*.mp. (259,183)4 Child, Preschool/(1,015,179)5 infant*.mp. or exp Infant/(1,419,667)6 Intervention Studies/or intervention*.mp. (1,272,614)7 Observational Study/or observational.mp. (186,994)8 randomised controlled trials as topic/or epidemiologicresearch design/or cross-over studies/(302,583)9 comparative study/or evaluation studies/ormeta-analysis/(2,466,746)10 Qualitative Research/or qualitative.mp. (253,593)11 Attitude to Health/or attitude*.mp. (586,720)12 Decision Making/or decision*.mp. (611,254)13 uptake.mp. (506,659)14 1 or 2 or 3 (629,636)15 4 or 5 (1,921,801)16 6 or 7 or 8 or 9 or 10 (4,175,191)17 11 or 12 or 13 (1,636,383)18 14 and 15 and 16 and 17 (1432)ote. Databases searched : EBM Reviews – Cochrane Database of System-tic Reviews <2005 to December 2013>, EBM Reviews – ACP Journal Club <1991 toanuary 2014>, EBM Reviews – Database of Abstracts of Reviews of Effects <1st Quar-er 2014>, EBM Reviews – Cochrane Central Register of Controlled Trials , EBM Reviews – Cochrane Methodology Register <3rd Quarter 2012>, EBMeviews – Health Technology Assessment <1st Quarter 2014>, EBM Reviews – NHSconomic Evaluation Database <1st Quarter 2014>, Embase <1996 to 2014 Week6>, Ovid MEDLINE(R) <1946 to January Week 5 2014>. PRESSxxx (2015) xxx–xxxauthor, with uncertain citations discussed with J.M. Full-textreports were gained for all eligible studies. The reference lists ofincluded studies were additionally searched for any relevant arti-cles. A sample of studies was independently assessed for eligibilityby J.M. to corroborate study selection. Any disagreements wereresolved by discussion. Studies were eligible for inclusion in thesystematic review if they reported interventions aimed at parentsof children (≤5 years-old) due or overdue one or more routineimmunisations, recommended to be administered by WHO, withoutcomes that measured child immunisation uptake. Because ofvariations in the reporting of immunisation uptake [3] outcomesthat addressed the uptake of individual or a combination of recom-mended vaccines were included. Studies without a control groupand studies that did not provide outcome data in terms of thenumber of children completely immunised or up-to-date for theirage were excluded from the meta-analysis. Interventions that metthese criteria but for which only one study was found were alsoexcluded from pooled analyses.2.3. Data extraction and assessment of methodological qualityStudy characteristics were recorded using a pre-defined dataextraction sheet. Information was extracted on (a) study design, (b)country of study, (c) intervention (including type, population, set-ting, details and sample sizes), (d) outcomes (including the numberof children completely immunised for their age, received at leastone dose of the studies vaccine(s), or were vaccinated on-time), (e)study findings and (f) eligibility for inclusion within meta-analyses.2.4. Risk of bias in individual studiesRisk of bias was performed by the primary author using theCochrane Collaboration Risk of Bias Tool [13]. Studies were assessedas being at a high, low or unclear risk of six attributes: sequenceallocation, allocation concealment, blinding, incomplete outcomedata, selective reporting, and other sources of bias. Studies wereassessed as ‘unclear’ when an attribute (e.g., blinding) was notor insufficient evidence to support a judgement was provided.Evidence of quality across studies was determined by the pro-portion of studies given each judgement for each methodologicalattribute assessed in the tool. Although assessment of study qualityis reported here it was not used to weigh review findings.2.5. Data analysisStudies that were eligible for inclusion in the meta-analysiswere grouped according to intervention type. Separate meta-analyses were conducted for each intervention type. Studiesexamining multiple interventions could contribute to several anal-yses. Where trials had a cluster randomised design, reportedintra-cluster correlation coefficient (ICC) were sought. If ICCswere not reported, unadjusted values were included in the meta-analyses, accepting that this might overestimate the weight of thesestudies in the analysis. Risk difference values and 95% confidenceintervals were used to calculate both individual and pooled effectsizes for the effect of each intervention on complete childhoodimmunisation uptake. Potential differences between studies wereexplored by sub-group analyses including where possible, the effectof the country of study income, time, frequency and method ofintervention delivery and focus of intervention content.Heterogeneity was assessed using Cochrane’s Q statistic, withp < .10 denoting heterogeneity. Inconsistency across studies was recall and educational interventions to improve early childhoode (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085measured using the I2 statistic, with a value greater than 40%presenting evidence of moderate heterogeneity and signalling theneed to use a random effects model [13]. Where heterogeneity wasnot reduced by sub-group analyses, variability in study methodARTICLE ING ModelJVAC-16417; No. of Pages 19H. Harvey et al. / Vaccine 1577 arti cles identi fied th roug h database searching (1432 OV ID; 145 EBSC Ohost )40 additio nal articles ide ntifie d through SRs and reference lists 499 dupli cat es re moved 1078 records screened 1040 irrelevant articles excluded 86 full-text articles assessed for eligibility fr om da tabase search 46 articles included in systematic review 28 artic les included in meta -32 artic les exc luded using eligibili ty criteria 18 artic les exc luded from me ta-analysis wetb33rmTFodtfiiwml3tiUecaatanalysi s Fig. 1. Flow diagram of study selection.as discussed. Evidence of publication bias was investigated byxamining the symmetry of the funnel plot and quantified usinghe Egger statistic, with p < .05 denoting evidence of publicationias. All analyses were performed using StatsDirect [14].. Results.1. Selection of studiesThe literature search generated 1577 articles. Following theemoval of duplicates, 1040 of the remaining 1078 articles did noteet the inclusion criteria based on an appraisal of the abstract.his resulted in 86 full-text articles, which were examined in depth.orty additional articles were identified from the reference listsf eligible papers and eight systematic reviews identified in theatabase search [3,6,9–11,15–17]. One hundred and twenty-six fullext reports were examined, and 48 qualitative studies removedor later qualitative analysis. Based on the criteria cited above, 32ntervention studies were ineligible, leaving 46 articles suitable fornclusion in the systematic review. Of these, a further 13 articlesere excluded because of inadequate study designs and outcomeseasures, and 5 [8,18–21] because of a lack of comparable trials,eaving 28 articles suitable for meta-analysis (Fig. 1)..2. Characteristics of studies included in the meta-analysisTable 2 summarises the characteristics of studies included inhe systematic review and meta-analysis. Of the studies includedn the meta-analysis (n = 28), 16 studies were conducted in thenited States, 5 in the UK or Republic of Ireland, 2 in Pakistan and 1ach in Australia, Ghana, India and Japan. Twenty-four randomisedPlease cite this article in press as: Harvey H, et al. Parental reminder,immunisation uptake: A systematic review and meta-analysis. Vaccinontrolled trials (RCTs), three cluster RCTs and one sequentiallyllocation control trial were included. One cluster RCT [22] reportedn ICC of zero. Consequently, no adjustment was made for clus-ering and clustering had no impact upon any findings reported. PRESSxxx (2015) xxx–xxx 3The studies included a total of 14,936 parent–child dyads whoseimmunisation uptake was assessed. Eight studies had data on thecomplete uptake of both DTP and Measles vaccines; 12 on DTP; 5on MMR; and 1 each on DTP and OPV; Hib, HBV and PCV7; and DTPand HepB.Each of the studies evaluated some form of parental reminderand/or education. These were grouped into six interventiontypes: (a) postal reminders [23–33]; (b) telephone reminders[25,26,29,32,34]; (c) combined recall and reminder [25,26,32,35];(d) education [22,30,31,36–42]; (e) education and reminder[30,31,43–45]; and (f) lay health workers (LHWs) [46–49]. Studiesthat could not be included in the meta-analysis because of a lack ofcomparable trials investigated a variety of intervention methods.Interventions included home vaccination [8], financial incentives[19], individual case management [21], LHW-lead group discuss-ions [18] and being tracked and escorted to the clinic by an LHW[20].3.3. Risk of bias for individual studiesUsing the risk of bias tool, 12 studies (43%) were judged to havean overall high risk of bias, 4 (14%) as low risk, and 12 studies(43%) as unclear risk. Risk of bias judgements for studies includedin the meta-analysis are shown in Fig. 2. Nine studies were judgedto be at a high risk of selection bias, describing a non-random com-ponent in the sequence generation process [38,41], inappropriateallocation concealment [37,42], or both [26,30,31,44]. The blind-ing of parents and/or health professionals was not possible whereinterventions were provided face-to-face. Only six studies includeda blind outcome assessor. In the majority of studies, blinding wasunclear or judged to be of high risk because those administering theintervention also assessed outcomes [22,30,31,36–38,40,44,48]. Inthe majority of studies, insufficient information was reported toprovide a judgement regarding blinding. Approximately 10% ofstudies [36,38,46] were judged to be at high risk of attrition biasowing to high rates of exclusion and loss to follow-up. Only threestudies [22,40,42] referred to protocols, so for the majority of stud-ies it was unclear whether selected reporting had been an issue.No evidence of publication bias was found for included studies: foreach pooled analysis, funnel plots were symmetrical, with studiespublished in each quarter of the plot. The associated Egger statisticswere non-significant in each case.3.4. Effectiveness of reminder-based interventionsThirteen studies evaluated the impact of one or more methodsof parental reminder. Pooled risk differences were calculated forthe effect of postal and telephone reminders, as well as studies thatutilised both methods in one study arm.3.4.1. PostalEleven studies (1 sequentially allocated control trial, 10 RCTs)examined the effectiveness of postal reminders [23–33]. In allstudies, parents were sent a letter or postcard reminding themthat their child’s immunisations were due or overdue. Interventiongroups within one study [24] examining personal and non-personalreminders were pooled to summarise the overall effect of inter-vention. The pooled fixed effect showed that postal reminderssignificantly improved immunisation uptake by 10.6% (RD = 0.106;95% CI = 0.080–0.131; p < .001; Fig. 3a). However, individual stud-ies reported a range of findings (from a 1.8% decrease to a 27.2% recall and educational interventions to improve early childhoode (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085increase) and substantial heterogeneity (I2 = 76.3%), indicating thatthe fixed effect model is unreliable. Using the random effectsmodel, the positive effect of postal reminders remained significant(RD = 0.099; 95% CI = 0.045–0.152, p < .001).Please cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 194 H. Harvey et al. / Vaccine xxx (2015) xxx–xxxTable 2Study characteristics.Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)Reminder-based interventionsAbramsonet al.[35], USARCT Postal andtelephonereminderInfants born at ForsythMemorial Hospitalreceiving primary carefrom 1 of 2 health centresA: Postcard reminder + telephonefollow-up (n = 302)Control: Routine care. No reminder(n = 299)Intervention: Postal reminder sent 1week before appointment and again ifappointment missed. Families thentelephoned every week until the childhad been vaccinated, the family movedhealth care provider or the infant was>1 month behind the scheduleComplete age-appropriateimmunisation by 2, 4 and 6monthsPostal remindersignificantly increaseduptake compared toroutine careYesAlemi et al.[50], USANon-randomisedcontrol trialTelephonereminderMothers with infants <6months attendingPaediatric practice whowere seen by 1 of 3participating paediatriciansand practice nursesA: Computer-reminder (n = 124)Control: Routine care. No reminder(n = 89)Intervention: Computer telephonereminder attempted before scheduledappointment. If appointments weremissed, parents reminded torescheduleOn-time immunisation Computerisedreminders significantlyimproved on-timeimmunisationcompared to routinecareNo; outcomemeasure (on-timeimmunisation)Alto et al.[51], USAProspective cohortstudyPostal andtelephonereminderChildren between 2months and 7 years whowere behind schedule andenrolled at the familypractice residency clinicA: Postcard followed by telephonereminder after 6 weeks (n = 231)Control: Routine care. No reminder(n = 233)Intervention: Parents sent postcarddetailing immunisation schedule andurging them to make an appointmentat the clinic. Telephone calls weremade up to 3 times over an 8-weekperiod if children remainedunimmunised 6 weeks from initialcontactComplete age-appropriateimmunisation 8 months afterinterventionPostal followed bytelephone remindersignificantly increasesimmunisation uptakecompared to routinecareNo; study designAtchisonet al.[52], UKBefore and afterstudyPostal reminder All children between 0 and5 years attending 44 GPpracticesA: Standardised call/recall system(n = 32 practices)Control: No system implemented(n = 12 practices)Intervention: Postal reminders sent toall children who were due or overdueany immunisations. Overdueappointments were sent up to 3invitations to attend. 3rd timedefaulters were referred to the HV forfollow-upComplete immunisations at:1. 12 months for 3×DTaP/IPV/Hib2. 24 months for MMR1,Hib/MenC booster, PCV booster3. 5 years for DTaP/IPV/Hibpre-school booster and MMR2Post-implementation,uptake wassignificantly improvedfollowing postalremindersNo; study designBjornsonet al.[23],CanadaProspective RCT Postal remindercards314 parents of children due12 month MMR or 18month DTP/IPV/HibboosterA: Reminder card (MMR n = 153;DTP/IPV/Hib n = 152)Control: No reminder (MMR n = 155;DTP/IPV/Hib n = 154)Intervention: Bright-colouredreminder card posted 4 weeks beforeappointment reminding parents whichimmunisations were due and to makean appointmentInfant immunisation statusafter 2-month follow-up periodPostal reminders didnot significantlyimprove infantimmunisation statusby 2 years oldYesPlease cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 19H. Harvey et al. / Vaccine xxx (2015) xxx–xxx 5Table 2 (Continued)Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)Campbellet al.[24], USARCT Postal reminder Parents of new-bornsenrolled in Paediatric clinicwho did not receive carefrom the primary authorA: Letter reminder (n = 87)B: Post-card reminder (n = 96)Control: Routine care. No reminder(n = 105)Intervention: Reminders sent 1 weekbefore appointment and specified itsdate and time. Letters includedinformation on the benefits ofimmunisation in accordance with theHBMComplete uptake of 3× DTP by7 months of agePostcard and letterreminders did notsignificantly improveimmunisation uptakein comparison to thecontrol groupYesDini et al.[25], USARCT Telephone andpostal reminder1227 children 60–90days-old who had receivedthe first dose of DTP andPolio registered at 1 of 4public health practicesA: Telephone reminder followed byletterB: Telephone reminder onlyC: Letter reminder onlyn = 96) Control: Routine care. NoreminderIntervention: Telephone messages sent1 week before appointment andrepeated every of schedule and theimportance of immunisations. After the5th telephone attempt, letters posted 2days after the 1st missed appointmentin group C and every week in group AComplete uptake by 24 months Children in allintervention groupshad significantlyimprovedimmunisation ratescompared to childrenin the control group.There were nodifference inimmunisation ratesbetween the threeintervention groupsYesGoldsteinet al.[53], USACohort study Door-to-door recalland reminder510 families with 1075children <6 years living ininner city public housingPaediatric Immunisation Programme(PIP) outreach workers carried outdoor-to-door to ascertain childimmunisation status from records.Record form provided to caregiverdetailing current uptake and vaccinesdue in the futureFinal child immunisation statusbased on records categorisedas receiving all, none or someof: DTP, PCV, Hib, MMRVisits by an out-reachworkers significantlyimprovedimmunisation ratesfrom baselinemeasuresNo; study designHicks et al.[54], USABefore and aftercohort studyPostal reminder All children <35 monthsnot up-to-date registeredat a non-profit communityhealth centreIntervention: Up to 3language-appropriate postal remindercards sent to families. Postcards listedthe type and number of vaccines thechild needed and invited parents toattend the clinic. Postcards served as aphysician order to the nurse toadminister the vaccine (n = 240 atbaseline; 263 after intervention)Number (%) of childrencompletely immunised andup-to-date for their age pre-and post-interventionReminder cardssignificantly increasedimmunisation uptakeNo; study designPlease cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 196 H. Harvey et al. / Vaccine xxx (2015) xxx–xxxTable 2 (Continued)Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)Irigoyenet al.[26], USANon-randomisedcontrol trialPostal andtelephonereminderParents of childrenbetween 4 and 18 monthsattending hospital –Paediatric clinic in alow-income populationA: Postcard reminder (n = 314)B: Telephone reminder (n = 307)C: Postcard + telephone reminder(n = 306)Control: Routine care. No reminder(n = 346)Intervention: Postcards were sent 1week before appointments. A bilingualclerk telephoned parents up to 3 timeson the weekday evening before theappointmentComplete uptake of 4× DTP, 3×Polio, 1× MMRNo significantdifference in uptakewas found betweenintervention andcontrol groups.Reminders significantlyincreased uptake for asubgroup of childrenwho were notup-to-date at baselineYesIrigoyenet al.[27], USARCT Postal reminder Children aged 6–15 weeksattending 1 of 5community-basedpaediatric practices in aninner city communityA: Continuous postal reminder(n = 549) B: Limited postal (max. 3letters) reminder (n = 552) Control:Routine care. No reminder (n = 561)Intervention: Bilingual(English/Spanish) reminder cardsposted to parents who needed a repeatreminder for a previously missed doseor a reminder for a new dose.Complete uptake of 4x DTP, 3xPolio and 1x MMR.Postal reminders didnot significantlyincrease uptakecompared to routinecare.YesLeBaronet al.[34], USARCT Reminder recall byaudiodialer andLHW outreach3050 parent–child pairsborn between July 1995and August 1996A: Audiodialer only (n = 764)B: Outreach only (n = 760)C: Audiodialer + Outreach (n = 763)Control: Routine care (n = 763)Intervention: Audiodialer message left1 week before appointment andfollowed up with postcard if no contactmade. If child remained unvaccinated 6days after due date the messagerepeated every 6 days before anotherpostcard was sentComplete uptake of 4× DTP, 3×Polio, 1× MMR, 3× Hib by 24monthsChildren in theaudiodialer only groupwere significantlymore likely to havecompleted therecommended courseof immunisations by 24monthsYesLieu et al.[28], USARCT Postal reminder Parents of 20-month-oldchildren who had notreceived MMRA: Postal reminder (n = 153)Control: Routine care. No reminder(n = 136)Intervention: Personalisedcomputer-generated letter remindingparents their child was overdue forimmunisation and requesting them toschedule and appointmentMMR uptake by 24 months Significantly morechildren received MMRby 24 months in theintervention thancontrol group. Postalreminders significantlyimprovedimmunisation uptakeby 19%YesLieu et al.[55], USARandomised trial Postal andtelephonereminder752 unimmunised20-month-olds registeredwith a HMOA: Automated telephone message(n = 188)B: Letter (n = 188)C: Automated telephonemessage + letter after 1 week (n = 188)D: Letter + automated telephonemessage after 1 week (n = 188)Intervention. Letters werepersonalised, language-appropriateand stated the child was overduerecommended vaccines and detailingthe location of the nearest HMO.Telephone messages were read in alanguage chosen by the listenerThe receipt of any neededchildhood immunisation(s) by24 monthsReceipt of a combinedreminder strategyresulted in significantlygreater uptake ofneeded immunisationsthan receipt of a letteror telephone messagealoneNo; study designPlease cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 19H. Harvey et al. / Vaccine xxx (2015) xxx–xxx 7Table 2 (Continued)Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)MorganandEvans[29], UKRCT Postal reminder ortelephone inquiryto HVChildren born between1994 and 1995 who werebehind schedule at 9months or who had notreceived MMR by 21monthsA: Telephone call to HV (n = 153)B: Postal reminder + questionnaire(n = 159)Control: Routine care. No intervention(n = 139)Intervention: (A) Telephone calls weremade to HVs to confirm the childdetails and immunisation status. (B)Parents were sent a reminder letterand questionnaire asking about thechild’s immunisation status andreasons for non-complianceComplete uptake of theprimary immunisationschedule by 12 months orreceipt of MMR by 24 monthsNeither telephone callsto HVs or reminderletters had an effect onprimary immunisationor MMR uptakecompared to routinecareYesStehr-Greenet al.[56], USARCT TelephonereminderParents of 2-year-oldchildren attending 1 of 2public health centres dueDTP, OPV or MMR duringthe 6-week study periodA: Telephone reminder (n = 112)Control: Routine care. No reminder(n = 110)Intervention: Computer-generatedtelephone reminder message notifyingparents of necessary immunisationsand to make an appointment.Messages were made for 5 daysstarting the day before a child becamedue for immunisation. Calls wereattempted a maximum of 9 timesFrequency of on-timeimmunisation for DTP, OPV 1, 2or 3 and/or MMR within 1month of becoming due forimmunisationTelephone reminderssignificantly increasedimmunisation uptakeby 2.8% compared toroutine careNo; outcomemeasure (on-timeimmunisation)Vivier et al.[32], USARCT Telephone and/orpostal reminder264 under immunisedchildren <6 years enrolledin Medicaid or uninsuredwith a family income<250% of federal povertylineA: Telephone reminder (n = 60)B: Mail reminder (n = 63)C: Sequential mail + telephonereminder (n = 70)Control: Routine care (n = 71)Intervention: Up to 3 telephone calls(group A) or a letter (group B)reminding parents their child’svaccines were overdue and to scheduleappointment. Parents in group C sentletter and telephoned after 1 week if anappointment remained unscheduledImmunisations received during10-month follow-upImmunisation status at the endof the follow-upReminder programmessignificantly improveduptake of anyimmunisations andbeing up-to-date.There was nodifference in uptakerates between thethree reminder groupsYesVora et al.[57], USANon-randomisedcontrol trialPostnatal healtheducation andreminder400 infants enrolled inMedicaidA: Hep B + immunisation education atbirth + reminder until uptake completeor infant 35 months (n = 400)Control: Citywide school entrants whocompleted kindergarten in 2001 and2002 from the same zip code asintervention population (n = 67, 376)Up-to date immunisations at 7,13, 19 and 24 months of ageCompleteness defined for 7and 13 months as: ≥2 HBV, ≥3DTaP, ≥3 Hib, ≥2 IPV; and ≥3HBV, ≥4 DTaP, ≥3 Hib, ≥3 IPVfor 19 and 24 monthsEducation fromoutreach-workerssignificantly improvedimmunisation uptakein high-risk childrencompared to controlsNo; study designYokley andGlenwick[58], USARCT Postal reminderand/or increasedaccess and/orincentive1133 under immunisedchildren <5 yearsA: Prompt giving general vaccineinformation (n = 195) B: Specificprompt naming child and vaccines(n = 190) C: Increased access (2xout-of-hours clinics) + specific prompt(n = 185) D: Monetary incentive(lottery entry upon visit) + specificprompt (n = 183) E: Contact control:telephone call detailing uptake(n = 189) F: No contact control: Routinecare (n = 191)Number of children receiving 1or more immunisations at theclinic Total number ofimmunisations received bytarget childrenAll interventionsexcept the generalprompt significantlyincreased uptake. Themonetary incentivehad the largest effectfollowed by increasedaccess, specificprompts.No; outcomemeasure (1 or moreimmunisations)Please cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 198 H. Harvey et al. / Vaccine xxx (2015) xxx–xxxTable 2 (Continued)Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)Young et al.[33], USARCT Postal reminder Children at risk of beingoverdue based on ≤1parent not educated pasthigh school, or 1 parentwith a college educationand ≥4 childrenA: Postal reminder (n = 253)Control: Routine care. No reminder(n = 254)Intervention: Letter posted to parentsof high-risk children who were 6months of age during the interventionperiod. The letter was intended toreduce immunisation dropouts andwas intended to act as a ‘motivation’ toreturn to the health centreChildren who received at leastone vaccineChildren bought up-to-datewith the recommendedschedule (3× DTP, 2× OPV)Significantly morechildren received avaccination following amotivational letter.More children werebought up-to-date inthe postal remindergroup but this did notreach significanceYesEducation-based interventionsBolam et al.[36],NepalRCT Postnatal healtheducationMothers living in 2communities served bygovernment fundedhospitalA: Education at birth in hospital + 3months at home (n = 135)B: Education at birth in hospital(n = 135)C: Education at 3 months at home(n = 135)Control: No education (n = 135)Intervention: 20 min one–one healtheducation discussion facilitated byquestions posed to motherComplete age appropriateimmunisation (1× BCG, at least2× DTP, 2× OPV) after 3- and6-month follow-upsMaternal education atbirth did notsignificantly increaseimmunisation uptakeof Nepalese childrenYesOwais et al.[37],IndiaRCT Postnatal healtheducation366 mother-infant pairs <6weeks living in 1 of 5low-income sitesA: Pictorial information cards (n = 183)Control: Verbal message about generalhealth promotion (n = 183)Intervention: 5 min session with CHWusing pictorial cards. Cards depictedinformation regarding the benefits ofvaccines, logistics surrounding clinicsand the need to retain immunisationrecords for school admissionImmunisation status ofDTP-3/HBV at 4 months afterenrolmentReceipt of pictorialinformation cardssignificantly improveduptake compared toroutine careYesPorter-Joneset al.[38], UKRCT Informative teddybear974 children due their 1stdose of MMR being seen bythe HV for routine 8-monthcheckA: Teddy bear + routine care (n = 542)Control: Routine care (n = 432)Intervention: Children given teddybear wearing a T-shirt that showed awebsite address that directed parentsto an NHS portal for MMR informationand the number of a telephone helplineUptake of the 1st dose of MMR Receiving a teddy bearwith MMR informationsources did notincrease uptake of the1st dose compared toroutine careYesQuinlivanet al.[39],AustraliaRCT Educational homevisits136 mothers attendingantenatal appointment atteenage pregnancy clinicA: Home visits + routine post-natalsupport (n = 65)Control: Routine post-natal support(n = 71)Intervention: 6 structured home visitsprovided by a midwife conducted at 1week, 2 weeks, and then bimonthly.Visits lasted 1–4 h and covered issuessurrounding breastfeeding,contraception and immunisationComplete uptake of allrecommended immunisationsat 6 monthsHome visits did notincrease immunisationuptake compared toroutine careYesPlease cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 19H. Harvey et al. / Vaccine xxx (2015) xxx–xxx 9Table 2 (Continued)Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)Saitoh et al.[40],JapanRCT Perinatal healtheducationMothers attending 1 of 3Obstetrics hospitalsA: Prenatal education at 34–36 weeksgestation (n = 34)B: Postnatal education 3–6 dayspost-delivery (n = 36)Control: Routine check up (36)Intervention: One-to-one interactiveeducational information onimmunisation, including: vaccinetypes, effectiveness, side effects andschedulingComplete uptake by 3 months Immunisation uptakewas significantlyhigher in theeducationalintervention groupscompared to thecontrol group. Therewere no significantdifferences in uptakebetween the pre andpostnatal educationgroupsYesShourieet al.[22], UKCluster RCT Decision aid forMMRParents with childrenbetween 3 and 12 monthsregistered at 1 of 50 GPpracticesA: MMR decision aid + routine care(n = 50)B: ‘MMR your questions answered’leaflet + routine care (n = 93)Control: Routine care (n = 77)Intervention: MMR decision aidcontained detailed information aboutthe risks and benefits of having and nothaving MMR and encouraged parentsto evaluate the information inaccordance with their valuesFirst dose MMR uptake by 15monthsICC estimated as zero, noadjustment for clusteringBoth interventionswere successful inreducing decisionalconflict but neithersignificantly improveduptake compared toroutine careYesStille et al.[41], USARCT Education 323 infants born atparticipating hospital whopresented to 1 of 3participating primary caresites <28 days oldA: Parental education + routine care(n = 156)Control: Routine care (n = 159)Intervention: Parents provided with agraphic card written in accordancewith the HBM depicting the primaryimmunisation schedules, and leavingspace to document child uptake alongwith general information. Providersalso explained the card and answeredany questionsComplete age-appropriateimmunisation by 7 monthsParental education didnot increase uptake by7 months compared toroutine careYesWilliamset al.[42], USACluster randomisedtrial (2 sites)Education Vaccine hesitant parentsattending 2 paediatricpractices for 2-weekwell-child visitsA: Parental education (n = 55)B: Routine care (n = 67)Intervention: Parental educationconstructed using the HBM containingan 8 min video describing commonconcerns amongst vaccine hesitantparents, and two leaflets about vaccineconcerns and how to find accuratemedical information on the InternetOn-time receipt of allrecommended vaccinations by2 monthsICC not reported, noadjustment for clusteringReceiving a briefeducational sessionsignificantly improveduptake compared toroutine careYesPlease cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 1910 H. Harvey et al. / Vaccine xxx (2015) xxx–xxxTable 2 (Continued)Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)Wroe et al.[59], NewZealandNon-randomisedcontrol trialAntenatal decisionaid100 women attendinghospital antenatal classesA: Decision aid (n = 50)Control: Standard immunisation leaflet(n = 50)Intervention: 20 page bookletcontaining detailed informationregarding the benefits/risks ofvaccines, the role of emotions (e.g.,omission bias) and the golden rule toencourage decision-making fromchild’s perspectiveNumber (%) of childrenimmunised on-time, late orunimmunised by 3 monthsA significantly higherproportion of infantswho received thedecision aid wereimmunised on timecompared to controlgroup infantsNo; outcomemeasure (on-timeimmunisation)Education- and reminder-based interventionsHawe et al.[43],AustraliaRCT Educational postalreminderParents of children born1987–1988A: HBM reminder card (n = 124)Control: Usual vaccination remindercard (n = 135)Intervention: Reminder cards wordedin accordance to the HBM. Cardsworded to prompt immunisation bystating (1) the severity of measles, (2)the susceptibility of children <2 yearsand (3) the risks of the diseaseoutweigh those of the procedurePercentage of childrenvaccinated againstmeasles/mumps in the 5 weeksfollowing postal reminderA significantly greaterproportion of childrenwere immunisedfollowing receipt of theHBM card compared tothe usual remindercardYesMason andDonnelly[45], UKRCT Postal reminderand informationChildren living in a healthauthority born betweenNovember 1996 and April1997 who had not receivedMMR by 21 monthsA: Postal reminder + informationalleaflet (n = 255)Control: Routine care. No reminder(n = 256)Intervention: Personal reminder lettersent to parents, GP and HV of child duefor immunisation. Parents also sent theleaflet MMR: the factsMMR uptake between 21 and24 months-oldPersonal reminderletters including aninformational leafletdid not increase MMRuptake compared toroutine careYesOeffingeret al.[44], USARCT Education andreminder238 mother–infant pairsdelivered by familypractice residentsA: Educational discussion + postalreminder (n = 116)Control: Routine care (n = 122)Intervention: 10–15 min discussion onthe 1st day postpartum with a nurse orphysician about the risks and benefitsof immunisation. Mothers also given1-page hand-out summarising pointsmade in the discussion and were sent areminder letter 2 months post deliveryComplete uptake of first 3doses of DTP/OPV by 1 yearPostnatal educationand reminder did notsignificantly improveuptake compared withroutine careYesUsmanet al.[30],PakistanRCT Immunisation cardand centre-basededucation1500 mother–child dyadsattending 5 urban EPIcentresA: Redesigned card (n = 375)B: Centre-based education (n = 375)C: Redesigned card + centre-basededucation (n = 375)Control: Routine care (n = 375)Intervention: Parents were given aredesigned reminder card detailingdate and location of their appointmentand instructed to place the card in avisible location and/or received a2–3 min education sessionemphasising the importance ofimmunisation at the EPI centreComplete uptake of 2nd and3rd doses of DTP at the end of90 day follow-upImmunisation uptakewas significantlyimproved in allintervention groups.Reminder cards andcentre-based parentaleducation significantlyincreased uptakeYesPlease cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 19H. Harvey et al. / Vaccine xxx (2015) xxx–xxx 11Table 2 (Continued)Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)Usmanet al.[31],PakistanRCT Immunisation cardand centre-basededucation1506 mother–child dyadsattending 6 rural EPIcentresA: Redesigned card (n = 378)B: Centre-based education (n = 374)C: Redesigned card + centre-basededucation (n = 376)Control: Routine care (n = 378)Intervention: Parents were given aredesigned reminder card detailingdate and location of their appointmentand instructed to place the card in avisible location and/or received a2–3 min education sessionemphasising the importance ofimmunisation at the EPI centreComplete uptake of 2nd and3rd doses of DTP at the end of90 day follow-upImmunisation uptakewas significantlyimproved in allintervention groups.Reminder cards andcentre-based parentaleducation significantlyincreased uptakeYesLay Health WorkersBarneset al.[46], USABefore and afterRCTEducation by LHWs 434 parent–child pairs at 1of 2 paediatric centres whowere <2 years-old andbehind scheduleA: LHW home visits (n = 218)Control: Reminder at enrolment visit(n = 216)Intervention: LHW home visitsprovided immunisation education andclinic referral, followed by 6-monthreminder periodComplete age-appropriateimmunisation after 6-monthfollow-up periodLHW home visitssignificantly improvedimmunisation uptakein the interventiongroup compared toroutine careYesBrugha andKevany[47],GhanaCluster RCT Home visits byLHW60 clusters containing36–39 residencescontaining children 12–18months-oldA: Survey + clinic referral and homefollow-up (n = 200)Control: Survey only (n = 219)Intervention: Child immunisationstatus established by interview andclinic referral made. Advice targeted toparents of incompletely immunisedchildren. Nurse followed upnon-attendance up to 3 times in 6monthsImmunisation coverage atcompletion of home visitintervention based on healthrecord and mother’s history.No ICC reported to adjust forclusteringMean immunisationsignificantly higher inthe 30 interventionclusters (clinic referraland home follow-up)than the control groupclustersYesJohnsonet al.[48],IrelandRCT Education by LHWs 262 first time mothersliving in a deprived areaA: Home visits from ‘Communitymother’ + Routine care (n = 141)Control: Routine care (n = 121)Intervention: Monthly visits from thecommunity mother providinginformation and guidance on childhealth and development, includingimmunisationsComplete uptake of primaryimmunisation schedule by 12monthsInfants whose mothersreceived home vestswere significantlymore likely to havecompleted theirprimary course ofimmunisations by 1yearYesNorr et al.[49], USARCT Home visits byLHW588 mother–infant pairsattending 1 of 2 prenatalclinics living in alow-income areaA: Home visits + routine care (n = 258;A-A = 182; M-A = 26)Control: Routine care (n = 219;A-A = 141; M-A = 78)Intervention: Monthly home visits bythe nurse and/or LHW 2 weeks afterhospital discharge to discuss childhealth and development. Home visitswere replaced by telephone calls after2 months if mother–infant pairs weredoing wellComplete uptake by 12 monthsdocumented by maternalreport and medical recordsImmunisation uptakenot significantlyimproved by homevisits compared toroutine care.Immunisation rateswere significantlyhigher in M-Acompared to A-AchildrenYesPlease cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 1912 H. Harvey et al. / Vaccine xxx (2015) xxx–xxxTable 2 (Continued)Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)Studies not included in the meta-analysisAnderssonet al.[18],PakistanCluster RCT LHW lead groupdiscussionIn each of the 32enumeration areas, 100children <60 monthsA: Community discussion + healtheducation programme (18 clusters)Control: Health education programme(14 clusters)Intervention: Three-phase communitybased discussion based on (1) theprevalence of childhood diseases, (2)costs and benefits to immunisation and(3) Community specific barriers andchallenges to uptakeUptake of measles and 3× DTPbetween 12 and 23 monthsImmunisation uptakewas significantlyhigher for children inthe communitydiscussion clustersthan clusters thatreceived healtheducation aloneNo; notcomparable withother studiesBanerjeeet al.[19], UKCluster RCT Incentive 30 households containingchildren aged 0–5 yearsrandomly selected from134 villagesA: Immunisation camp (30 villages,379 children)B: Immunisation camp + incentive (30villages, 382 children)Control: No camp or incentive (74villages, 860 children)Intervention: Monthly ‘immunisationcamp’ offering regular immunisationservices. Additional incentive offeredto group B consisting of 1 kg raw lentilsper immunisation administered and aset of metal plates upon completion offull scheduleComplete or partial uptake of1× BCG, 3× DTP, 3× OPV, 1×measlesSmall incentives toimmunise had agreater positive impact(RR = 6.7) on uptakecompared to improvingservices alone(RR = 2.2)No; notcomparable withother studiesBond et al.[8],AustraliaRCT Home vaccination Children 90 days late for3rd dose DTP/OPV/Hib or120 days late for MMRliving in 1 of 10 councilareasA: Home vaccination service (n = 81)Control: Routine care (n = 88)Intervention: Home vaccination at atime convenient to parentsComplete uptake ofDTP/OPV/Hib or MMRHome vaccinationsignificantly increasedimmunisation uptakecompared to routinecareNo; notcomparable withother studiesBond et al.[60],AustraliaCross-sectionalbefore and afterIncentive Children <3 yearsattending a registered childcare centreGovernmental parent incentivescheme. To receive childcare benefitsand Maternity Allowance parents mustdemonstrate complete immunisationof childProportion of children between1997 and 2000 who were: 1.Fully immunised; 3 milestonescomplete (1. 3× DTP, 3× Hib,3× OPV; 2. MMR; 3. DTP/Hib).2. Age appropriatelyimmunisedSignificantly morechildren were fullyimmunised in 2000following theintroduction of thegovernmentalincentive compared to1997 before it wasintroducedNo; study designCrittendenand Rao[61], UKBefore and afterstudyGeneralencouragementParents of non-attendingchildrenIntervention: Reasons fornon-compliance discussed with GP andHV before postal contact made. Ifnecessary a home visit was made todiscuss vaccination or administrationscheduled for a hospital visit (n = 93)Complete uptake of primaryvaccines or preschool boosterNo; study designPlease cite this article in press as: Harvey H, et al. Parental reminder, recall and educational interventions to improve early childhoodimmunisation uptake: A systematic review and meta-analysis. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 19H. Harvey et al. / Vaccine xxx (2015) xxx–xxx 13Table 2 (Continued)Study design Intervention type Population/setting Intervention Outcomes measured Summary of findings Included inmeta-analysis?(Yes/No; reason forexclusion)Fersonet al.[62],AustraliaRandomised trial(no control)School-nurse 239 incompletelyimmunised 5 year oldsattending 1 of 28 primaryschoolsA: Written material in appropriatelanguage (n = 119)B: Written materials + phone call 1–2months after information (n = 120)Intervention: Written material toencourage immunisation uptake.Telephone call established uptake orencouraged uptake in cases wherechild remained unimmunisedUptake of measles and/orbooster immunisationsclassified as complete, some ornoneSignificantly morechildren wereimmunised following atelephone callcompared to theprovision of writtenmaterials aloneNo; study designRodewaldet al.[20], USARCT Tracking withoutreach LHW andproviderprompting3015 infants attending 1 of9 primary care practicesborn between 01/03/1993and 28/02/1994A: Tracking/outreach + prompting(n = 732)B: Tracking/outreach only (n = 715)C: Prompting only (n = 801)Control: Routine care (n = 767)Intervention: Tracking/outreach wasprovided by LHWs who worked withparents of under immunised infants tobring them to the primary care officeusing postcards, telephone calls andhome visits. Prompting was providedby the primary care office that usedreduced missed opportunities byimmunising necessary childrenregardless of visit typeImmunisation status on thelast day of the interventionclassed as complete uptake forage-appropriate scheduleTracking/outreach andprompting significantlyincreasedimmunisation uptakeby 20% and reduced thedelay in immunisationby 63 daysNo; notcomparable withother studiesWood et al.[21], USARCT Case management 419 mother–infant dyadsliving in 1 of 10 enrolmentzip codesA: Case management + Health Passport(n = 209)Control: Health Passport only (n = 210)Intervention: In-depth assessment athome when infant <6 weeks andsubsequent visits 2 weeks beforescheduled appointment by casemanager. Managers providedinformation about immunisation andsought to overcome barriers such aslack of insurance and transportComplete immunisation by 12months defined as the receiptof 3× DTP, 2× OPV, 3× HibImmunisation uptakewas significantlyimproved by 13.2% inthe case managementgroup compared toroutine careNo; notcomparable withother studiesNote. DTP = Diphtheria, Tetanus, Pertussis; DTaP = Diphtheria, Tetanus, acellular Pertussis; IPV = inactivated Polio vaccine; OPV = oral Polio vaccine; Hib = Haemophilus influenzae type b; Hib/MenC = Haemophilus influenzae type band meningitis C; MMR = Measles, Mumps and Rubella; HBV = Hepatitis B vaccine; PCV = Pneumococcal vaccine; BCG = Tuberculosis vaccine; M-A = Mexican-American; A-A = African-American; HBM = Health Belief Model.ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 1914 H. Harvey et al. / Vaccine xxx (2015) xxx–xxx1631861017825713127439640% 20% 40% 60% 80% 100%Other sources of biasSelectiv e reporting (reporting bias)Selective outcomes (attrition bias)Blind ing (performan ce/ detection bias)Allocation Concealment (selection bias )Random Sequence Allocation (selection bias)Low risk of bias Unclear risk of bias High risk of biasF ers at aibatr(maCicnpRu3eTeouaCym3apTpi(gisig. 2. Risk of bias chart for studies included in the meta-analysis (n = 28). Numbttribute in the tool.Sub-group analyses were performed according to the personal-sation and focus of postal reminders to explore the heterogeneityetween studies. Sub-group findings also displayed heterogeneitynd hence, random effects models are reported. Results suggest thathe specificity of postal reminders did not influence efficacy, as allesults were similarly positive. Both personal [23,24,26–28,30,31]including the child’s name, immunisations due and/or appoint-ent detail; n = 7; RD = 0.112; 95% CI = 0.037–0.187, p = .004)nd non-personal reminders [24,25,29,32,33] (RD = 0.075; 95%I = 0.024–0.125, p = .004) were associated with a significantncrease in uptake. Likewise, letters that were targeted (recall) tohildren overdue their scheduled vaccines or those at a high-risk ofon-compliance [27–29,32,33] (RD = 0.091; 95% CI = 0.030–0.153, < .001), and those that were not [23–26,30,31] (reminder;D = 0.10; 95% CI = 0.020–0.190 p < .001) had a positive effect onptake..4.2. TelephoneFive studies (1 sequentially allocated control trial, 4 RCTs)xamined the efficacy of telephone reminders [25,26,29,32,34].elephone calls were made and/or messages were left with par-nts to remind them that their child’s immunisations were due orverdue. As heterogeneity was minimal, a fixed effects model wassed. Receiving a telephone reminder (Fig. 3b) was associated with significant 4% increase in immunisation uptake (RD = 0.040; 95%I = 0.006–0.073, p = .019). One large study [34] dominated the anal-sis. Heterogeneity of findings was low and thus a random effectsodel produced similar findings..4.3. Combined postal and telephone (recall and reminder)Four studies (1 sequentially allocated control trial, 3 RCTs)ssessed the impact of receiving a postal reminder letter and tele-hone prompt on childhood immunisation uptake [25,26,32,35].he fixed effect model found that the receipt of both postal and tele-hone reminders (Fig. 3c) was associated with a significant 10.6%mprovement in immunisation uptake compared with controlsPlease cite this article in press as: Harvey H, et al. Parental reminder,immunisation uptake: A systematic review and meta-analysis. VaccinRD = 0.106; 95% CI = 0.070–0.143, p < .001). Substantial hetero-eneity was found between the studies, with individual study find-ngs ranging from a 3.2% to 18.9% increase in uptake, meaning theize of the effect cannot be accurately determined. Nevertheless,the end of each bar show the number of studies within each judgement for eachuse of combined reminders remained significant using a randomeffects model (RD = 0.113; 95% CI = 0.033–0.193, p < .006).One study [26] was methodologically different from others inthe group because it used a combination of postal and telephonereminders to inform parents of their child’s appointment beforethey were due, whereas the remaining studies used one methodto inform parents of their child’s appointment details (recall),and only used another method if children remained unimmunisedafter 1 week (reminder). Excluding this trial reduced heterogeneity(I2 = 31.6%), while the overall effect remained similar (RD = 0.147;95% CI = 0.10–0.195, p < .001).3.5. Effectiveness of education-based interventionsSeventeen studies evaluated the impact of parental education.Pooled risk differences were calculated for the effect of educationalinterventions, education and reminder and the support of a LayHealth Worker (LHW).3.5.1. Immunisation educationTen studies (2 cluster RCTs; 8 RCTs) examined the effectof providing parents with immunisation-based education[22,30,31,36–42]. Parents were advised about immunisationor general child health before their child’s immunisation appoint-ment. Education was facilitated by a discussion with a trainedprofessional, or by written information in picture card or leafletformat. One study provided parents with the details of how toaccess several written educational sources. Two studies includedintervention groups who received education at different timepoints; intervention groups are pooled for these trials [36,39]. Theoverall fixed effect suggests that parental education significantlyimproved immunisation uptake by 8.3% (Fig. 4a; RD = 0.083; 95%CI = 0.056–0.110, p < .001). However, findings from individualstudies ranged from a 1.6% decrease to 26% increase in immun-isation uptake and substantial heterogeneity was found in thedata. A random effects model reported a similar average effect of recall and educational interventions to improve early childhoode (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085intervention (RD = 0.078; 95% CI = 0.013–0.142, p = .018).Heterogeneity was explored by sub-group analyses performedaccording to study country income, intervention timing, frequencyand method. Similar levels of heterogeneity were found, thusARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 19H. Harvey et al. / Vaccine xxx (2015) xxx–xxx 15r-baseroaRvotuFig. 3. Remindeandom effects models are reported. The overall effects of studiesffering parental education at birth [36,40–42] (infant < 1 month)nd post-natally [22,30,31,36–38] (infant > 1 month) were similar.esults suggested that the efficacy of educational interventionsPlease cite this article in press as: Harvey H, et al. Parental reminder,immunisation uptake: A systematic review and meta-analysis. Vaccinaried between low- and high-income countries, and the methodf education used. LMIC studies [30,31,36,37] found educationo be significantly more effective than routine care, improvingptake by 13% (RD = 0.13; 95% CI = 0.05–0.22, p = .002), whiled interventions.those in HICs [22,38–42,63] were not found to be consistentlyeffective. Discussion-based interventions [30,31,36,39,40] sig-nificantly improved uptake by 12% compared to routine care(RD = 0.12; 95% CI = 0.02–0.21, p = .014). Interventions providing recall and educational interventions to improve early childhoode (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085parents with written educational information [22,37,38,41,42]were not found to be effective. Study numbers were too small toexplore interactions between country income and interventionmethods.ARTICLE IN PRESSG ModelJVAC-16417; No. of Pages 1916 H. Harvey et al. / Vaccine xxx (2015) xxx–xxx-base3ptfFig. 4. Education.5.2. Immunisation education and postal remindersPlease cite this article in press as: Harvey H, et al. Parental reminder,immunisation uptake: A systematic review and meta-analysis. VaccinFive RCTs examined the efficacy of interventions that providedarents with some form of immunisation education in addi-ion to a postal reminder [30,31,43–45]. The fixed effect modelound parental education and postal reminders (Fig. 4b) led tod interventions.a 16% increase in uptake (RD = 0.16; 95% CI = 0.12–0.19, p < .001), recall and educational interventions to improve early childhoode (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085although with substantial heterogeneity. Individual study findingsranged from 1% to 26% improvements, with the two largest studiesreporting the greatest effect, being conducted in Pakistan [30,31].A positive effect of education and postal reminders remained, ING ModelJccine up3p[hhosmsid9tai4pptTttcgrpirwtfttTinvHbertnititwmlwpmonmARTICLEVAC-16417; No. of Pages 19H. Harvey et al. / Vasing a random effects model (RD = 0.13; 95% CI = 0.01–0.25, = .04)..5.3. Support from Lay Health Workers (LHWs)Four studies (1 cluster RCT, 3 RCTs) examined the impact ofarental education about immunisation and advice from a LHW46–49]. For the purposes of this review, LHWs were defined as aealth worker providing education about immunisation, but whoad not received any formal healthcare training. LHWs comprisedf volunteer mothers, O-level graduates and community workers. Aignificant effect of LHWs (Fig. 4c) was found using the fixed effectsodel (RD = 0.10; 95% CI = 0.05–0.15, p < .001). However, individualtudy findings were mixed (ranging from a decrease of 3% to anncrease of 20%) and substantial heterogeneity was found. A ran-om effects model did not reach statistical significance (RD = 0.11;5% CI = −0.02 to 0.25, p = .09). Sub-group analyses accounting forhe specificity of LHW advice found that specific immunisationdvice [46,47] was associated with a significant 17% increase inmmunisation uptake (RD = 0.17; 95% CI = 0.10–0.24, p < .001).. DiscussionThere is evidence to support the efficacy of postal and/or tele-hone reminders, parental education, and parental education withostal reminders for improving child immunisation uptake.Reminder-based interventions were significantly more effec-ive than routine care independent of their method of delivery.his finding is comparable to that of a previous Cochrane reviewhat found that reminder systems were efficacious for immunisa-ion uptake across the lifespan [9]. The present review however,onducted separate meta-analyses for individual reminder strate-ies specific to childhood immunisations and found that postaleminders were more effective than telephone reminders. Henceostal reminders are recommended for use in primary care tomprove childhood vaccine uptake. Moreover, postal and telephoneeminders had an additive impact on uptake; their combined useas associated with a greater increase in immunisation uptake thanhe use of each strategy alone. However, this effect could be an arte-act of the more intensive recall-reminder strategies used in theserials and suggests that recall strategies may be particularly effec-ive in parents whose children may be at risk of non-attendance.here is a need for future research to explore the efficacy of thisntervention in trials comparing children at high and low risk ofon-compliance.The overall group analysis suggested that educational inter-entions significantly increased childhood immunisation uptake.owever, sub-group analyses suggested that this effect was driveny two factors: (a) the study occurring in an LMIC and (b) par-nts having a discussion with a professional expert, rather thaneceiving information in written form. Analysis did not suggest thathe timing or intensity of education impacted upon its effective-ess. The baseline education levels of the participants enrolled inncluded studies may explain the increased efficacy of interven-ions conducted in LMICs. Approximately 50% of mothers enrolledn studies within this comparison were illiterate or had no educa-ion. Secondary levels of maternal education have been associatedith a two-fold increase in childhood immunisation compared toothers with no education [63]. Interventions that raise the basicevel of parental knowledge are therefore more effective in areashere understanding is low compared to countries where it is com-aratively higher and educational barriers to immunisation may bePlease cite this article in press as: Harvey H, et al. Parental reminder,immunisation uptake: A systematic review and meta-analysis. Vaccinore subtle and linked to vaccine belief [2,4]. Contrary to a previ-us meta-analysis [11,64], the overall effectiveness of LHWs couldot be recommended following the application of a random effectsodel [20,34,46–49]. Sub-group analyses did suggest that parents PRESSxxx (2015) xxx–xxx 17who received specific vaccine support from an LHW might be moreeffective than general support that did not extend beyond topicscovered by health visitors in routine care, suggesting an avenue forfuture research.Keys to the efficacy of discussion-based educational inter-ventions may come from qualitative findings that suggest thatdiscussion with a trusted medical practitioner may facilitateimmunisation compliance owing to the depth and clarity of under-standing gained compared to the reported overwhelming natureof written information leaflets [65–67]. These findings suggestthat providing parents with the opportunity to discuss immu-nisations in detail with a healthcare professional may furtherfacilitate immunisation rates. However, due to the additionalhuman resources needed to incorporate practitioner-lead discus-sion within primary care settings, policy planners may be mindfulto reserve these strategies for vaccine-hesitant parents.The overall utility of educational strategies within standardpractice may be further questioned when examined alongside theresults of trials that provided parents with both immunisation edu-cation and appointment reminders. Using the same methods inboth rural and urban settings, the two Usman et al. trials [30,31]examined education and reminder strategies in separate and com-bined study arms. In both communities, improvements of uptake ingroups who received the combined intervention were minimal incomparison to postal reminders alone. This finding has implicationsfor policy as it suggests that reminder systems may be sufficientfacilitators of childhood immunisation in the majority of cases, andthat discussion-based strategies may be most effective in familieswith children at high-risk of non-compliance. Such strategies mayincrease compliance because they acknowledge parental concernsabout vaccination. Addressing these concerns in a discussion witha medical professional regarding the risks and benefits of vacci-nation may change the parental attitudes, knowledge and beliefsabout vaccination. Changes in attitude may facilitate behaviourchange; facilitating a pro-vaccination decision further facilitatessubsequent vaccine uptake. However, the effectiveness of suchstrategies must be tested in future trials.4.1. Strengths and limitationsWhilst the findings of this review help to summarise the largebody of literature on parental interventions for childhood immun-isation uptake, several limitations were apparent. First, substantialheterogeneity was evident in all of the comparisons except tele-phone reminders. Although random effects models were utilisedto investigate the mean distribution of underlying interventioneffects, such models do not identify reasons for variation. Unex-plained heterogeneity suggests there may be some differences instudy method and/or services provided that explain why inter-ventions were effective in some cases but not in others. Althoughthere were too few studies within the published research sampledto explore this formally, the effect of differences in study contextcan be illustrated by the two Usman et al. studies [30,31]. Thesestudies utilised the same method of allocation, intervention strat-egy and outcome measure but were conducted in urban and ruralareas of Pakistan respectively. However, they found a 12.8% dif-ference in immunisation uptake of parents who received postalreminders in favour of rural communities, suggesting factors notreported such as access to, and interaction with, healthcare servicesmay contribute to the success of interventions. Owing to the lim-its of journal space, the authors were unable to provide additionaldetail regarding risk of bias judgements for individual studies and recall and educational interventions to improve early childhoode (2015), http://dx.doi.org/10.1016/j.vaccine.2015.04.085excluded studies however; such details are available on request.Variation between studies may also explain the discrepancybetween the results of the present study and two previous reviewson LHWs [11,65]. The present review examined the effects of ING ModelJ1 ccine e[Ifseataaicdctcrhm4tsivattisowRafpCR[[[[[[[[[[[[[[[[[[[[[[[[[[[ARTICLEVAC-16417; No. of Pages 198 H. Harvey et al. / Vaducation provided by LHWs and therefore did not include two20,34] out of four studies [20,34,46,48] previously analysed.nstead, two additional studies [47,49] were included. This dif-erence and the high levels of heterogeneity found betweentudies in each review may explain this disagreement and furtherxaggerates the limited conclusions that can be made by presentlyvailable studies in the field.Second, many of the strategies used in reminder-based interven-ions may not be relevant to the parents of today. Mobile phonesre owned by large majorities of people living in major countriesround the world, 75% of whom use their mobile phones for text-ng [68]. For example, 96% of mobile phone owners in Indonesia, aountry where less than 50% of children do not receive the threeoses of DTP [2], use their mobile phones to text. The increasingommonality of access to technology including mobile phones andext messaging may offer increased effectiveness in terms of out-ome and cost. Several small-scale studies have linked text messageeminders to improvements in both adolescent [69,70], and child-ood [71] immunisations. However, larger RCTs are necessary toake firmer conclusions about the efficacy of such interventions..2. ConclusionsThe findings of this review suggest that several interven-ions, particularly postal reminders, combined recall and remindertrategies and discussion-based education, can increase childhoodmmunisation uptake. The precise effectiveness of these inter-entions is likely to be influenced by numerous factors suchs country of intervention and levels parental vaccine hesitancyhat need to be explored by future trials. This review highlightshe potential benefits to childhood vaccine uptake of incorporat-ng parental interventions, particularly postal reminders into thetandard management of childhood immunisations, and the usef recall strategies and/or discussion-based forums with parentshose children are at high risk of non-compliance.ole of the funding sourceThis work was supported by a studentship from the Economicnd Social Research Council awarded to the primary author. Theunding source had no involvement in the design, analysis or inter-retation of the findings presented in this report.onflict of interestNone declared.eferences[1] Plotkin SL, Plotkin SA. A short history of vaccination. In: Plotkin SA, OrensteinWA, Offit PA, editors. Vaccines. Philadelphia: Sanders, Elsevier; 2008. p. 1–14.[2] WHO, UNICEF, World Bank. State of the world’s vaccines and immunization.3rd ed. Geneva: World Health Organisation; 2009.[3] Kaufman J, Synnot A, Ryan R, Hill S, Horey D, Willis, N, et al. 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