Effectiveness of Catch-Up Vaccination Interventions Versus Standard or Usual Care Procedures in Increasing Adherence to Recommended Vaccinations Among Different Age Groups: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Before-After Studies

Background: To address the global challenge of vaccine hesitancy, the Strategic Advisory Group of Experts on Immunization strongly promotes vaccination reminder and recall interventions. Coupled with the new opportunities presented by scientific advancements, these measures are crucial for successfully immunizing target population groups. Objective: This systematic review and meta-analysis aims to assess the effectiveness of various interventions in increasing vaccination coverage compared with standard or usual care. The review will cover all vaccinations recommended for different age groups. Methods: In February 2022, 2 databases were consulted, retrieving 1850 studies. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, 79 manuscripts were included after the assessment phase. These comprised 46 trials/randomized controlled trials (RCTs) and 33 before-after studies. A meta-analysis using a random-effects model was performed with STATA software (version 14.1.2). The selected outcome was the risk ratio (RR) of vaccination coverage improvement effectiveness. Additionally, meta-regression analyses were conducted for the included manuscripts. Results: The analyses showed an overall efficacy of RR 1.22 (95% CI 1.19-1.26) for RCTs and RR 1.70 (95% CI 1.54-1.87


Introduction
The immunization programs are specifically designed to maximize the health benefits for the population by offering the most appropriate vaccinations for different age groups and types of patients [1].The effectiveness of vaccination programs is based on a high uptake level.In addition to providing direct protection for vaccinated individuals, these programs offer indirect protection to the community by decreasing the risk of infection [2].
Although vaccination is one of the most successful public health interventions, global immunization coverage rates remain unsatisfactory.In 2021, nearly 25 million children under the age of 1 year missed their routine diphtheria-tetanus-pertussis vaccinations.Additionally, human papillomavirus (HPV) vaccination coverage among girls in the least developed countries was only 15% [3].Undervaccination can be attributed to a lack of health services available to the population, lower availability of vaccines for mass immunization programs, and difficulties in accessing these services in terms of both space and time [4].Insufficient budgets are one of the main barriers preventing health governments from providing access to mass vaccination in low-income countries [5].
Although the health governments of the most developed countries are strongly implementing national immunization programs, introducing new vaccines, and expanding vaccination offers, coverage rates are still far from desirable targets.This shortfall has resulted in outbreaks of vaccine-preventable diseases, leading to hospitalizations and, in some cases, death [6,7].The literature examining the acceptance of routine vaccinations for adolescents (such as the HPV vaccine) and vaccines recommended for older adults or those with chronic and disabling conditions (such as influenza, pneumococcal, and herpes zoster vaccines) indicates critical issues with uptake [8,9].Vaccine hesitancy, defined as "the reluctance or refusal to vaccinate despite vaccine availability," has gained recognition as a top threat to global health because it could undermine successful and cost-effective vaccination programs worldwide [10].The main factors contributing to vaccine hesitancy are a lack of awareness about the benefits of vaccination, concerns regarding short-or long-term side effects of vaccines, general distrust in immunization practices, and doubts about the high number of vaccines administered according to schedules [11].Furthermore, the growing complexity of vaccination programs, with the introduction of new vaccines and the high number of recommended booster doses, could represent an obstacle to achieving optimal coverage.This complexity can cause difficulties in adherence and delays in vaccinating the target population [12].
The decline in vaccinations threatens to strain health systems with outbreaks of vaccine-preventable diseases.Several attempts have been made to identify approaches that increase immunization coverage, such as vaccine information campaigns, promotional and educational messages for patients and health care professionals, and the use of reminders and various mobile apps [12,13].Active vaccine catch-up interventions can be an extremely useful tool for improving adherence to vaccination practices.Experience and research can help identify the most effective vaccination strategies.
This systematic review and meta-analysis aims to evaluate vaccine adherence across various catch-up methods targeting different age groups.Additionally, we aimed to identify the most effective vaccination recall strategies compared with standard or usual care procedures, based on randomized controlled trials (RCTs) and before-after studies.

Study Guidelines
For this systematic review, we followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis; Multimedia Appendix 1) statement guidelines [14] to ensure transparency and thorough reporting of both the review process and results.The review protocol was registered on PROSPERO under the registration number CRD42022307311 and it can be accessed online [15].

Search Strategy and Selection Criteria
Two literature databases, PubMed/MEDLINE and Scopus, were utilized for this review.The literature search commenced on February 14, 2022, using a combination of free-text words and Medical Subject Headings (MeSH).The search strategy incorporated general terms such as "vaccine," "effectiveness," and "improvement," along with specific terms related to catch-up intervention implementation.The search strings obtained are detailed in Multimedia Appendix 2.
The Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria were applied to select studies, encompassing populations of all ages without restrictions on country or length of follow-up.Eligible participants were those eligible for vaccination and receiving a catch-/mop-/keep-up intervention involving reminders or recalls.The objective was to evaluate the intervention-dependent vaccination coverage improvement effectiveness (VCIE), which is a composite outcome created by assessing both the improvement in vaccination coverage and the completion of vaccination series, in comparison to standard vaccination practices.During both the screening and assessment phases, authors excluded research articles based on the following criteria: if the topic or outcome did not align with the review's objective, if the study did not use an RCT or before-after study design, if the studies lacked vaccination coverage data, or if there were insufficient data regarding the "before" or "control" group or description of catch-up/recall intervention.
Study-level data were recorded in Excel spreadsheets (Microsoft Excel 2010).Risk ratios (RRs) and corresponding 95% CIs of VCIE were directly calculated to evaluate the effect of different intervention types on the receipt of immunizations.Separate analyses were conducted for RCTs and before-after studies.If data on the main outcome (VCIE) were available from more than 1 study, a random effects model meta-analysis was used to pool the data.The results were stratified based on the "intervention category" variable, and pooled RRs and risk differences were computed for each intervention category.These analyses were conducted using STATA software (version 14.2.1;StataCorp).Between-study variation was estimated by comparing each study's result with a Mantel-Haenszel fixed-effect meta-analysis.The extent of heterogeneity was quantified using I 2 .Testing for publication bias was conducted separately for RCTs and before-after studies for the main outcome.Additionally, meta-regression analyses were performed using the following summary measures: an estimate of between-study variance (tau), the proportion of between-study variance (adjusted R 2 ), the percentage of residual variation due to heterogeneity (I 2 ), and a joint test for all covariates (model F) with Knapp-Hartung modification (prob>F).

Overview
A total of 1869 research articles were identified from the literature databases, with 1784 (94.45%) retrieved from the PubMed/MEDLINE platform and 85 (4.55%) from Scopus.After removing duplicates (n=22), 1847 records underwent screening based on titles and abstracts.Among these, 239 full-text articles were assessed for eligibility, and ultimately, 79 studies were included in the data extraction and qualitative synthesis.Specifically, 46 (58%) of these studies were RCTs, and 33 (42%) were before-after studies included in the meta-analysis.The main reasons for excluding studies were as follows: outcomes not aligned with the review's interest (n=56) and studies not utilizing an RCT or before-after study design (n=29).A summary of the screening process and exclusions is depicted in the PRISMA flow diagram (Figure 1).

Characteristics, Quality Score, and Results of Meta-Analysis and Meta-Regression for RCT Studies
Of the included RCTs, 20 studies (43%) were conducted in the American continent, with 18 of them (39%) in the United States.Additionally, 11 studies (24%) were conducted in Asia and 9 studies (20%) in Europe.Only 5 studies (11%) were conducted in Africa and 1 study was conducted in Australia.Regarding the age groups targeted by the interventions, the studies were most frequently focused on the "infant-preschool" category in 46% of cases (n=21), followed closely by the "child-adolescent" category in 43% of cases (n=20).The "middle-aged adult" category was addressed in 15% of studies (n=7).According to the classification of intervention types, "multicomponent" studies were identified most frequently, accounting for 48% (n=22) of the total.Following this, "educational" studies comprised 24% (n=11) of the included studies.The "reward" category was the least represented, with only 4% (n=2) of the studies falling under this category.Among the reminder interventions, the "clinical" and "messaging" subcategories were the most populated, accounting for 22% (n=10) and 28% (n=13) of the included studies, respectively (Table 1).

Characteristics, Quality Score, and Results of Meta-Analysis and Meta-Regression for Before-After Studies
Among the 33 before-after studies included, 42% (n=14) were conducted in the American continent, predominantly in the United States (n=13, 39%).Europe accounted for 30% (n=10) of the studies, followed by Asia with 15% (n=5) of the studies.Additionally, 9% (n=3) of the studies were carried out in Africa (Egypt, Kenya, and Nigeria), while only 3% (n=1) were conducted in Australia.
The most prevalent "age categories" were the "child-adolescent" category, accounting for 58% (n=19), followed by the "adult-middle age" category, which comprised 39% (n=13) of the studies.
The scoring system used to assess bias in before-after studies examined various items, with 1 additional point assigned each time the item in question was present.The items in question were clearly stated study question or objective (32/33 studies, 97%); prespecified and clearly described eligibility/selection criteria for the study population (28/33, 85%); study participants representative of those who would be eligible for the test/service/intervention in the general/clinical population of interest (28/33, 85%); whether all eligible participants who met prespecified entry criteria were enrolled (15/33, 45%); sample size large enough to provide confidence (18/33, 55%); test/service/intervention clearly described and delivered consistently across study population (17/33, 52%); prespecified, clearly defined, valid, reliable, and consistently assessed outcome measures across all study participants (19/33, 58%); people who assessed outcomes blinded to participant exposures/interventions (0/33, 0%); losses to follow-up after baseline 20% or less and whether those lost to follow-up were considered in the analysis (19/33, 58%); presence of changes in outcome measures from pre-to postintervention with P values statistically examined for pre-post changes (27/33, 82%); and outcome measures taken several times before the intervention/after the intervention (15/33, 45%).The evaluation of the quality score of the before-after studies revealed that 8 studies attained the maximum score of 8.Among these, 4 were categorized as "educational" [66-69], 2 as "multicomponent" [70,71], and 2 as "reminder clinical" [72,73].By contrast, the lowest score of 4 was assigned to 2 studies: 1 categorized as "reminder clinical" [74] and the other as "reminder messaging" [75] (Table 5).
The meta-analyses results for before-after studies indicated a statistically significant RR of 1.70 (P<.001).Subgroup analyses, as detailed in Multimedia Appendix 5, revealed that the most efficacious intervention reported was the "reminder active call" intervention (RR 2.19; P<.001), followed by "educational" (RR 2.16; P<.001) and "multicomponent" (RR 1.61; P<.001) interventions.Heterogeneity and significance tests for the type of intervention are provided in Multimedia Appendices 6-8.
Meta-regression analyses were conducted for before-after studies, incorporating the following variables: quality score, publication year, continent, GNI, age category, intervention type, and follow-up time since the intervention.The variable  Table 5.The scoring system a used for before-after studies.
h Were the outcome measures prespecified, clearly defined, valid, reliable, and assessed consistently across all study participants?i Were the people assessing the outcomes blinded to the participants' exposures/interventions? j Was the loss to follow-up after baseline 20% or less?Were those lost to follow-up accounted for in the analysis?k Did the statistical methods examine changes in outcome measures from before to after the intervention?Were statistical tests done that provided P values for the pre-to-post changes?l Were outcome measures of interest taken multiple times before the intervention and multiple times after the intervention (ie, did they use an interrupted time-series design)?m N/A: not applicable.

Principal Findings
Catch-up vaccination strategies are crucial components of a comprehensive national immunization program and should be continually integrated [99,100].Understanding the effectiveness of vaccination interventions is essential for selecting those best suited to diverse sociodemographic contexts.Therefore, this research included RCTs and before-after studies, recognized as effective catch-up strategies.
In general, catch-up interventions identified in the studies, categorized into 4 groups ("multicomponent," "educational," "remind," and "reward studies"), demonstrated effectiveness in promoting adherence to vaccination.However, practices associated with certain types of "reward" interventions did not exhibit statistical significance [37,38].Reminder and recall interventions are used to prompt individuals within a target population regarding upcoming vaccinations (recall) or overdue vaccinations (reminder).These strategies vary in content based on the type of vaccination and the target demographic.They are implemented through various methods, including telephone calls with active reminders; messaging via SMS text messages, emails, or traditional mails; in-person reminders within clinical settings; the use of physical objects as reminders; and reminders via web-based platforms.Active call interventions have been shown to significantly enhance vaccination adherence rates.This is likely because telephone contact provides direct access to health care professionals who can address patients' concerns and inquiries.Moreover, active calls serve as a reminder tool that is easily accessible and adaptable, even in resource-constrained settings.For instance, a study conducted in Nigeria demonstrated that vaccination uptake doubled among newborns whose mothers received calls from health care workers at vaccination centers [34].
Vaccination reminder interventions conducted through messaging (SMS text messages, emails, letters, and notifications) are also effective, although they tend to have a lesser impact compared with "active calls" [36].This could be attributed to the limitations of "messaging reminders"

XSL • FO
RenderX interventions, such as the inability to engage in immediate question-and-answer discussions with health care workers and the challenge of personalizing the SMS text message, which is often predefined and sent using automated software [41].Despite the limitations, the widespread use of mobile technologies enables rapid and effortless communication with large communities of people.Additionally, considering the low cost and ubiquity of mobile phones, "messaging reminders" could prove to be an excellent strategy for implementation, especially in low-and middle-income countries [54,63].
Another highly effective strategy for increasing vaccination coverage is the "clinical-remind" approach, where all vaccination promotion interventions occur directly within hospital or primary care settings.Offering vaccination to patients during hospital visits for examinations, consultations, or treatments is a strategy endorsed by the World Health Organization (WHO) to minimize missed opportunities for vaccination.This approach aims to enhance health care service delivery and foster seamless collaboration among health care professionals [101].A randomized study conducted in Georgia in 2018 serves as a demonstration of this strategy.In the study, the tetanus, diphtheria, and pertussis (Tdap) vaccine was offered to pregnant women during gynecological visits in antenatal clinics.Results indicated a higher willingness to receive vaccination among pregnant women in the intervention group compared with the control arm [56].Presently, the Advisory Committee on Immunization Practices (ACIP) recommends that pregnant women receive the Tdap vaccine during each pregnancy, regardless of their immunization history [102].Despite recommendations, maternal Tdap vaccination coverage remains low, not only in the United States but also in many other parts of the world.However, evidence suggests that vaccination strategies involving patient engagement in a clinical setting can effectively increase coverage [56].
The results further highlight the effectiveness of "educational interventions" in vaccine catch-up efforts.Health education stands as one of the primary tools for ensuring that a population has access to health care services.As early as 1983, the WHO recognized health education as a universal right of communities [103].This right can be realized through integrated information and education programs, aiming to enhance both the population's desire for good health and their ability to discern the validity of the information they receive [104].Lack of knowledge and misinformation stand as the primary barriers impeding widespread access to vaccination [12].Addressing these challenges necessitates a shift toward a more suitable educational approach within the vaccination context.Particularly, among the selected educational interventions, those based on face-to-face dialog between patients and health care professionals emerge as the most effective.An RCT conducted in Italy, aimed at evaluating the impact of various types of educational programs targeting the adolescent population, demonstrated that face-to-face lessons are more effective in increasing vaccination coverage compared with web-based lessons [45].
A highly effective strategy for boosting vaccination coverage is the multidimensional approach, which emerged as the most frequently utilized in the studies included in this review.This approach encompasses interventions that combine vaccination reminder tools with awareness sessions and patient education on vaccination.These interventions are implemented through multiple steps and in various formats.According to the Strategic Advisory Group of Experts on Immunization (SAGE), "multicomponent" interventions are more effective than those with a single component.By addressing various aspects, they are more successful in enhancing knowledge and awareness and in fostering psychological shifts and attitude changes toward vaccinations [104].A compelling example comes from a before-after study conducted at a rheumatology clinic in Illinois, United States.This study implemented a multifaceted intervention, which included electronic reminders with linked order sets, physician auditing, and patient outreach, resulting in improved patient vaccination rates [86].
The meta-regression analysis indicated a higher effectiveness of vaccination interventions in the European continent compared with other geographic regions.This finding is likely a reflection of the disparity in economic resources and access to health care services between high-income and low-middle-income countries [4].There is no one-size-fits-all approach to vaccine catch-up that proves effective across all contexts and realities.This is especially true for developing countries, where scientific evidence remains limited.Many vaccine interventions in the WHO African Region, reviewed by the SAGE to develop guidelines addressing vaccine hesitancy, are often documented in the gray literature, which was not encompassed in our review [104].However, this research has unveiled findings that hold potential global relevance.For instance, health strategies centered around reminders have proven to be effective and cost-efficient, making them particularly suitable for countries with limited resources [54].Conversely, the significant success observed in certain vaccination programs conducted in the European continent underscores the importance of evaluating the performance of vaccination services in these countries [45,79,83,97].As of now, there remains a lack of standardized protocols for immunization services aimed at monitoring and improving service quality.Progress in this area has stagnated since the drafting of the National Vaccine Advisory Committee's standards for vaccination services in the 1980s [105].However, some authors have proposed models to develop accreditation manuals for vaccination services.These manuals would establish a minimum set of quality standards to ensure the delivery of high-quality preventive health care services.Such standards are crucial for optimizing service effectiveness and ensuring the efficient allocation of economic resources toward public health initiatives [106,107].
Finally, the meta-regression results also revealed the effectiveness of various interventions aimed at vaccination catch-up among a specific demographic: middle-aged adults.This finding may be attributed to the organization of vaccination services by age group.Historically, the majority of vaccines have been developed for pediatric populations, and extensive national and international collaborative efforts have strongly supported mass immunization of the youngest individuals, even in developed countries, to ensure adequate access to life-saving vaccines.Moreover, childhood vaccination programs are typically uniform, well-defined, and bolstered by annual XSL • FO RenderX monitoring of vaccine dissemination and its impact on reducing morbidity and mortality.Conversely, reaching the adult population with standard vaccine delivery methods can be more challenging.However, catch-up vaccination and recall interventions have the potential to be highly effective in enhancing coverage among adults.
The older age population, aged 65 years and over, faces a lack of dedicated vaccination programs tailored for their age group, despite being the demographic most vulnerable to the risks and complications associated with infectious diseases [108].In 2009, 2 geriatric societies, the European Geriatric Medicine Society (EUGMS) and the International Association of Gerontology and Geriatrics-European Region (IAGGER), formulated guidelines outlining recommended vaccinations for the geriatric population.Despite these efforts, the vaccination provision for older patients continues to vary widely among different European countries [109].The ongoing challenge is to develop vaccination programs for older adults that are as comprehensive and effective as those designed for children.
Moreover, numerous vaccination catch-up interventions rely on "reminder" strategies, which entail sending SMS text messages or emails and providing information through dedicated web pages [25,35,97].While the utilization of mobile technologies can be a significant asset for vaccination strategies targeting adolescents and adults, it may pose a challenge for the older age population.Alternative intervention modalities may thus prove more suitable.For instance, a study conducted in France aimed at offering recommended vaccinations to hospitalized patients demonstrated a significant increase in vaccination coverage [57].Providing vaccination counseling in hospital or outpatient settings could be the most effective strategy for achieving widespread vaccination among the older age population.

Comparison With Prior Studies
We identified several prior meta-analyses, published between 2017 and 2018, that investigated the impact of vaccine interventions targeting specific population groups or focused on particular types of interventions [3].Although patient reminder and recall systems have been extensively studied, the existing literature does not provide data on the potential impact of other vaccine catch-up interventions [110].Moreover, the search strategy for this systematic review was not confined to any specific geographical context or timeframe, nor was it designed to target a particular type of vaccination.Our study offers an analysis of various vaccination strategies, enabling the identification of the most suitable interventions for each population and vaccination category, across diverse sociodemographic contexts.

Limitations
The search strategy for this systematic review did not encompass gray literature documents and reports.Although the investigation covered all geographical contexts, the majority of the selected and included studies were conducted in developed countries.This bias may arise because some studies on vaccinations and recall interventions in developing countries are typically found in gray literature.Furthermore, no vaccination catch-up interventions related to the COVID-19 vaccine were included.The COVID-19 vaccination, being introduced during an emergency pandemic situation, is not part of the scheduled vaccination regimen.Despite these limitations, this study is among the first to investigate a broad array of vaccine catch-up strategies for scheduled vaccines, encompassing recent studies targeting all age groups of the population.

Conclusions
Vaccination reminder interventions, incorporating educational sessions for the population and utilizing various reminder methods such as SMS text messages and calls, as well as multifaceted interventions combining multiple strategies, have demonstrated effectiveness in enhancing vaccination coverage.However, it is important to note that there is no universal catch-up strategy that performs well across all contexts and realities.It is essential to adopt the most suitable intervention strategy based on the patient category, resource availability, and the socioeconomic status of the target population to be vaccinated.

Figure 1 .
Figure 1.PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) flow diagram of studies selection.
The overall results of meta-analyses for all RCT studies demonstrated an RR of 1.22 (P<.001), indicating an increase in VCIE across all types of interventions included in the RCT sample.Further details on heterogeneity and significance tests for all intervention categories are provided in Multimedia Appendix 3. The most effective interventions are extensively detailed in Multimedia Appendix 4, which includes the forest plot of RCTs.The highest efficacy was reported for "multicomponent" interventions, with a risk ratio (RR) of 1.58 (P<.001) (see Figure S1A in Multimedia Appendix 4), followed by "reminder clinical" studies, which exhibited an RR of 1.24 (P<.001; see Figure S1B in Multimedia Appendix 4).Furthermore, "educational" interventions (RR 1.15; P<.001) and "reminder messaging" interventions (RR 1.14; P<.001) demonstrated a positive effect on VCIE.Forest plots summarizing results for other types of recall interventions can be found in Figure S1C, D in Multimedia Appendix 4.

[ 97 ]
Poscia et al[91] Costantino et al[79] Gattis et al[72] Wallace-Brodeur et al[68] Glanternik et al[80] Kaufman et al[71] Costantino et al[69] JMIR Public Health Surveill 2024 | vol. 10 | e52926 | p. 20 https://publichealth.jmir.org/2024/1/e52926(page number not for citation purposes) point for the appropriate item, 0 points if inappropriate.A negative score is not expected.b Was the study question or objective clearly stated?c Were eligibility/selection criteria for the study population prespecified and clearly described?d Were the participants in the study representative of those who would be eligible for the test/service/intervention in the general or clinical population of interest?

Table 1 .
Characteristics of RCT included studies.aVariables reported were author's first name, publication year, country, recruitment study year range, follow-up period since the intervention, outcome(s), intervention type and category, mean age range among controls/interventions, and number of enrolled patients.b dTPa: diphtheria, tetanus, and acellular pertussis. a

Table 2 .
The scoring system a used for randomized controlled trials.

Table 3 .
Meta-regression of randomized controlled trials.
a Statistically significant results.

Table 6 .
Meta-regression of before-after studies.
a Statistically significant results.