In this critical appraisal and synthesis of evidence, the authors will utilize the mixed-methods approach. This approach has been shown to combine pieces of evidence from qualitative, quantitative, and other mixed-methods studies to successfully provide more seamless and scientific findings on selected topics [17, 18]. Data triangulation, a feature of the mixed-methods approach, has improved the validity of systematic reviews by increasing the scope, depth, and consistency in systematic review methodologies [19]. The methodological approach of this study will permit the use of the qualitative findings to either clarify or contradict the quantitative findings in an explanatory format [20]. The review is expected to commence in July 2021. The protocol has been registered at the Open Science Framework (Registration DOI: https://doi.org/10.17605/OSF.IO/BVP4S).
Criteria for Studies Inclusion
Interest Population
The review will focus on studies conducted on individuals who are concerned with vaccination activities and programs. The population subgroups will not be limited to:
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Adults (18 years and above) who are potential targets of vaccination programs. For example; travelers who are required by immigration policies to vaccinate against diseases such as yellow fever.
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Children below 18 years, provided parental consent was obtained before their inclusion.
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Healthcare workers, including professionals who are tasked with vaccination.
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Parents/guardians who are to ensure their wards complete vaccination schedules. For example; vaccination schedules targeting childhood vaccine-preventable diseases.
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Vaccination policy-makers. For example; public health professionals who formulate immunization policies for governments and organizations.
The population-specific characteristics of studies that would be included in the review will take into account the age of study subjects, their ethnic backgrounds, and other sociodemographic features of the study subjects.
Phenomenon of Interest
Vaccine hesitancy is the phenomenon of interest for this review. The outright refusal of vaccination interventions and/or the undue delay in accepting vaccination interventions regardless of the availability of immunization services characterizes vaccine hesitancy [21]. Therefore, the research team will consider for inclusion, studies that focused on vaccine hesitancy.
Context of Study
The review will focus on primary vaccine hesitancy studies conducted in low- and middle-income countries according to the World Bank classification. The low- and middle-income countries would include the 29 low-income countries, the 50 lower-middle-income countries, and the 56 upper-middle-income countries. Therefore, the review will consider vaccine hesitancy studies conducted in these 135 countries. The characteristics of the study findings table will reflect these three (3) World Bank income level subgroups and hence, a subgroup analysis will be done [22].
Outcomes of Interest
The facets of vaccine hesitancy that will be studied include; the causes of vaccine hesitancy, the reasons why individuals who reside in LMICs delay and/or reject vaccination services, and the various measures that have been taken by vaccination agencies to address the issue of vaccine hesitancy.
In reporting on the causes of vaccine hesitancy, the review team will screen included studies for causes such as the influx of misleading information about vaccination, the unstable supply of vaccines, poor energy supply which affects cold-chain storage of vaccines, and the poor availability of trained vaccination staff. The reasons behind vaccine hesitancy will be reviewed from the perspective of individuals who are potential targets of vaccination services. Some of the reasons that will be considered include the fear of adverse vaccination reactions, distrust in the effectiveness of vaccines, inconveniencies encountered at vaccination centers, and superstitious beliefs surrounding vaccination services. Measures that have been successful in addressing vaccine hesitancy will not be limited to education and the adequate supply of vaccines.
Potential studies to be considered
The review team will consider quantitative, qualitative, and mixed-methods primary studies for possible inclusion.
Quantitative studies will not be limited to descriptive studies and cross-sectional studies. All primary studies that are quantitative in their design will be considered. The qualitative arm of the review will consider all forms of interviews, all forms of group discussions included focused-group discussions, observational studies, and other studies that were conducted following the principles of qualitative study design. Primary studies that combined the principles of qualitative and quantitative study designs will constitute the mixed-methods arm.
Criteria for Studies Exclusion
Studies that will be excluded from the review, with grounds of exclusion, include:
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secondary studies including all forms of reviews and overviews.
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editorials, commentaries, conference proceedings, letters to the editor, position statements of organizations, and expert opinions. This is because they are not primary studies.
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book chapters. This is because they do not meet the requirements of primary studies.
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primary studies that are pre-prints or in-press. This is because they have not completed the publication process and hence, have not been rigorously peer-reviewed.
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abstracts only studies. These studies do not have the full component of primary studies suitable for a systematic review.
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primary research articles that do not have abstracts. This is because subjecting such studies to titles and abstracts screening will not be possible.
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studies that were conducted in high-income countries. Including such studies will be contrary to the defined context of the review.
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primary studies that were not reported in the English language. The review team is only fluent in the English language. Therefore, the team will not be able to review studies that were not published in the English language.
Proposed databases and respective search strategies
The review will recruit studies published by journals indexed in Medline, CINAHL, and Web of Science. Except for Web of Science, which will be sourced directly, Medline and CINAHL will be sourced via EBSCOhost. Search strategies for the proposed databases have been developed by EW and reviewed by KBM for the identification of various literature. The preliminary search strategies have been tested by EW and the numerical results of the individual databases have been presented, see Appendix A.
The development of the search strategy took into consideration the PICO framework [23, 24] outlined in the criteria for study inclusion. The keywords of the review also guided the development of the search strategy. The preliminary search strategies were developed according to the three-step procedure employed by Wiafe and his team members (2020) [23].
The application of the search strategies to identify and extract potential studies will be done by KR and DT for Medline, SM and NB for CINAHL, and NM and TS for Web of Science. The reviewer pairs would work independently to improve the quality of the database search, and their results would be pulled by SD in the EndNote reference manager (version X8). The EndNote library manager, SD, will identify and remove duplicates to present a final catalog of search findings for the review. The duration for the database search would span from the inception of the proposed databases to June 30, 2021.
Titles and abstracts screening
The titles and abstracts screening would be done after the identification and removal of duplicates. This activity would be performed independently by three reviewers (KR, DT, and SM). The eligibility criteria would serve as the yardstick for the titles and abstracts screening of studies. Potential studies that will pass this quality assurance stage will thereafter undergo full-text screening. Any disagreements that would arise between the three independent reviewers will be settled in discussion with SD. In instances where the inputs of SD are not appreciated by KR, DT, and SM, FO would be consulted to settle the disagreement.
Full-text screening
Studies that would pass the titles and abstracts screening will be subjected to the full-text screening by three reviewers (NB, NM, and TS) who would function independently. The full-text screening will aim at ensuring that the eligibility criteria are firmly applied to the studies to reduce the risk of errors in this evidence synthesis [25]. In addressing disagreements as part of the quality assurance processes, the approach employed during the titles and abstracts screening would be relied on.
Quality assessment and final inclusion of studies
The quality appraisal tool used by Bangura and colleagues (2020) [26] when they studied the obstacles to childhood vaccination, see Appendix B, will be employed to assess the quality of studies that will pass the full-test screening. This quality appraisal tool has been modified and the assessment criteria have been increased from 14 to 15. The modification was aimed at ensuring the ease of scoring and the interpretation of scores as indicated on the attachment: Appendix B. The quality appraisal of studies will be done independently by KBM and EW. The settlement of disagreements, however, will be settled by FO without the involvement of SD because of the extensive experience of FO. None of the research papers will be excluded based on the methodological quality evaluation outcome.
Data extraction and results
The extraction of data from included studies will be done by six reviewers (second to seventh authors) and the eighth will recheck for the completion and accuracy of data. The issues of data inconsistency due to disagreements between the six reviewers will be addressed by FO. Two data extraction tools have been designed, with guidance from other systematic reviews [26, 27], for this review. Namely; Table 1: Characteristics of Included Studies, and Table 2: Summarized Study Findings.
Table 1
Characteristics of Included Studies
Author, year
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Study Country (and World Bank Income Level)
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Research Question(s) or Objective(s)
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Research Methodology
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Sociodemographic Features of Participants
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Duration of Study (Years)
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Methodological Quality Score (and Interpretation)
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Sample Size (and Study Population)
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Table 2
Summarized Study Findings
Study Title
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Response Rate (%)
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Determinants of Vaccine Hesitancy
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Conclusions
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Limitations
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Causes of Vaccine Hesitancy
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Reasons for Vaccine Hesitancy
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Successful Control Measures of Vaccine Hesitancy
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The first table of results will have the following details about the included studies: the author and year, the study country (and world bank income level), the research question(s) or objective(s), the research methodology, the sociodemographic features of participants, the duration of the study (years), the methodological quality score (and interpretation) and the sample size (and study population). To obtain data, which is lacking, SD will contact the corresponding authors of the included studies through their electronic mails. Upon the lack of response, after a month’s wait, such need for data will be regarded as “missing”.
The summarized study findings’ table will highlight details of included studies such as; the study title, the response rate, and the determinants of vaccine hesitancy which has three facets (the causes of vaccine hesitancy, the reasons for vaccine hesitancy, and the successful control measures of vaccine hesitancy). The concluding remarks of the authors of the included studies and the limitations of these studies will be documented as part of the study findings.
A PRISMA flowchart diagram will be presented, as a figure, as part of the results of the review. The flowchart will highlight the reasons behind the exclusion of studies, and a numerical presentation of records at each stage of the review will be presented. The reference list of included studies will be screened by SD for extra studies. These studies will be included after passing the laid out quality assurance processes and duly documented in the table of results and PRISMA flowchart diagram.
Analytic considerations
The analytic stage of the review will commence from the various quality assurance stages concerning the resolution of disagreements between the reviewers. An assessment for agreement or otherwise between reviewers, performing the same task, will be done to ensure that various outcomes are reliable and devoid of bias [28]. The kappa coefficient, a robust statistic, will be utilized in this assessment and a kappa coefficient of at least 0.6 will reflect an agreement between the independent reviewers.
A meta-analysis will not be performed because the review is not an interventional study and does not seek to assess the effectiveness of measures that addressed vaccine hesitancy. This is evident as a similar study by Bangura et al., (2020) did not lead to the conduct of a meta-analysis [26]. However, a subgroup description of results will be done. The studies will be grouped according to their quality assessment outcomes (weak, moderate, and strong), the age groups of study participants (below 18 years, and 18 years and above), and the World Bank financial classifications of the study sites (low-income countries, lower-middle-income countries, and upper-middle-income countries).
The Quan-qual data obtained from the included studies will be analyzed independently [29]. The evidence obtained from the independent synthesis of the quantitative and qualitative data will be integrated via configuration [30]. This process will permit the comparison of the quantitative evidence to the qualitative evidence, and attempt to address the various aspects of the outcomes of interest [30]. The outcomes of the review will be presented as a narrative [31].