Effect of PCV Dosing Schedules on Prevention of Pneumonia
Effect of PCV Dosing Schedules on Prevention of Pneumonia
This analysis is part of a larger project describing the impact of PCV dosing schedules on invasive pneumococcal disease (IPD), immunogenicity, nasopharyngeal carriage, pneumonia and indirect effects. Details on the literature search terms and methods used in this systematic review are described elsewhere (see Methods Appendix). In brief, a systematic literature review was performed to collect all available English language data published from January 1994 to September 2010 (supplemented post hoc with studies from 2011) on the effect of various PCV vaccination schedules among immunized children on immunogenicity, nasopharyngeal colonization, IPD, pneumonia and on indirect effects among unvaccinated populations. Articles published in 14 databases, from ad hoc unpublished sources and abstracts from meetings of the International Symposium on Pneumococci and Pneumococcal Disease (1998–2010) and the Interscience Conference on Antimicrobial Agents and Chemotherapeutics (1994–2010), were searched. We included all randomized controlled clinical trials (RCTs), nonrandomized trials, surveillance database analyses and observational studies of any PCV schedule on one or more outcomes of interest. Studies were included for abstraction if pneumococcal polysaccharide vaccine (PPV23) was used as a booster dose, but not as a primary dose. Titles and abstracts were reviewed twice and those with relevant content on 1 of the 5 outcomes (immunogenicity, carriage, invasive disease, pneumonia and indirect effects) underwent full review using a standardized data collection instrument. We did not search non-English language literature because of the low likelihood they would have relevant data for this project. Details on the search methods are provided in the Methods Appendix.
Citations recovered through the literature search went through several stages of independent review to determine their eligibility, as described (see Methods Appendix). Citations meeting inclusion criteria were categorized on an outcome-specific basis into "study families," where each family included abstracts or publications generated from a single protocol, population, surveillance system or other data collection system relevant to that outcome. Investigators identified primary data from the individual studies making up each study family for inclusion in the analysis. The primary data were selected as the most current and complete data available for that study family. In some cases, these data were drawn from >1 publication within a family. We also defined "study arms" as a group of children distinguished by immunization schedule or PCV product.
We abstracted core information on the following: number of children in a "study arm;" PCV manufacturer, valency and conjugate protein; co-administered vaccines; country; age at each dose and date of study and publication. Additional data abstracted for pneumonia included specific endpoints, case definitions, study design, study population and incidence rates or percent change.
This article presents the data on the direct effects of PCV on pneumonia in children of an age targeted for vaccination. As studies included a variety of case definitions for endpoints, findings were grouped by endpoint according to the following categories: clinical pneumonia (including lower respiratory tract infections and acute respiratory tract infections), radiologically confirmed pneumonia, pneumococcal pneumonia (including bacteremic pneumonia) and empyema.
We included data published during or after 1994 from clinical trials, surveillance database analyses and observational studies of PCV schedules on immunogenicity, IPD, nasopharyngeal carriage, pneumonia and indirect effects. We included all licensed and unlicensed PCV products (denoted as PCV with a number indicating the valency, eg, PCV7). We excluded studies with vaccination series beginning after 12 months of life, as well as observational studies that only reported data before or after PCV introduction but not for both periods. Unless ≥50% vaccination coverage was documented, observational studies were also excluded if vaccination was only available through the private sector or to high-risk groups. Studies that only provided incidence rates during the year of vaccine introduction, or did not specify a period, were excluded.
We defined a primary series as either 2 or 3 doses received before 7 months of age. A booster dose was defined as a dose of PCV or PPV23 received after 9 months of age and after the completion of a primary series. A complete series was defined as the primary series plus any booster doses implemented in a population; examples of this include a 2-dose primary series with or without a booster (2+1, 2+0) or a 3-dose primary series with or without a booster (3+1, 3+0).
Studies evaluating impact on pneumonia following PCV introduction used a variety of methods; the variety prevented us from performing a formal meta-analysis. Therefore, we conducted descriptive analyses of the amount and variability of the data and of the magnitude of the change in the pneumonia outcomes observed for each dosing schedule type. We also performed subanalyses to evaluate various endpoints related to pneumonia. Studies reporting only qualitative data with no ability to determine magnitude of impact were excluded from analysis.
For observational studies reporting pneumonia incidence over time, we calculated percent change as: (baseline incidence —post-PCV introduction incidence)/baseline incidence. Baseline incidence was defined as the mean of all data points reported before PCV introduction. When annual data on postintroduction incidence were available, we calculated percent change using the data point given for each year reported. When only the average postintroduction incidence rate over a period of years was provided, we calculated percent change from baseline to the reported rate and assigned it to the median year of the date range provided. When possible, incidence rates during the year of introduction were excluded from these calculations. We conducted all analyses using SAS 9.3 (SAS Institute Inc., Cary, NC).
Methods
Literature Search
This analysis is part of a larger project describing the impact of PCV dosing schedules on invasive pneumococcal disease (IPD), immunogenicity, nasopharyngeal carriage, pneumonia and indirect effects. Details on the literature search terms and methods used in this systematic review are described elsewhere (see Methods Appendix). In brief, a systematic literature review was performed to collect all available English language data published from January 1994 to September 2010 (supplemented post hoc with studies from 2011) on the effect of various PCV vaccination schedules among immunized children on immunogenicity, nasopharyngeal colonization, IPD, pneumonia and on indirect effects among unvaccinated populations. Articles published in 14 databases, from ad hoc unpublished sources and abstracts from meetings of the International Symposium on Pneumococci and Pneumococcal Disease (1998–2010) and the Interscience Conference on Antimicrobial Agents and Chemotherapeutics (1994–2010), were searched. We included all randomized controlled clinical trials (RCTs), nonrandomized trials, surveillance database analyses and observational studies of any PCV schedule on one or more outcomes of interest. Studies were included for abstraction if pneumococcal polysaccharide vaccine (PPV23) was used as a booster dose, but not as a primary dose. Titles and abstracts were reviewed twice and those with relevant content on 1 of the 5 outcomes (immunogenicity, carriage, invasive disease, pneumonia and indirect effects) underwent full review using a standardized data collection instrument. We did not search non-English language literature because of the low likelihood they would have relevant data for this project. Details on the search methods are provided in the Methods Appendix.
Data Abstraction
Citations recovered through the literature search went through several stages of independent review to determine their eligibility, as described (see Methods Appendix). Citations meeting inclusion criteria were categorized on an outcome-specific basis into "study families," where each family included abstracts or publications generated from a single protocol, population, surveillance system or other data collection system relevant to that outcome. Investigators identified primary data from the individual studies making up each study family for inclusion in the analysis. The primary data were selected as the most current and complete data available for that study family. In some cases, these data were drawn from >1 publication within a family. We also defined "study arms" as a group of children distinguished by immunization schedule or PCV product.
We abstracted core information on the following: number of children in a "study arm;" PCV manufacturer, valency and conjugate protein; co-administered vaccines; country; age at each dose and date of study and publication. Additional data abstracted for pneumonia included specific endpoints, case definitions, study design, study population and incidence rates or percent change.
This article presents the data on the direct effects of PCV on pneumonia in children of an age targeted for vaccination. As studies included a variety of case definitions for endpoints, findings were grouped by endpoint according to the following categories: clinical pneumonia (including lower respiratory tract infections and acute respiratory tract infections), radiologically confirmed pneumonia, pneumococcal pneumonia (including bacteremic pneumonia) and empyema.
Inclusion and Exclusion Criteria
We included data published during or after 1994 from clinical trials, surveillance database analyses and observational studies of PCV schedules on immunogenicity, IPD, nasopharyngeal carriage, pneumonia and indirect effects. We included all licensed and unlicensed PCV products (denoted as PCV with a number indicating the valency, eg, PCV7). We excluded studies with vaccination series beginning after 12 months of life, as well as observational studies that only reported data before or after PCV introduction but not for both periods. Unless ≥50% vaccination coverage was documented, observational studies were also excluded if vaccination was only available through the private sector or to high-risk groups. Studies that only provided incidence rates during the year of vaccine introduction, or did not specify a period, were excluded.
Pneumococcal Vaccine Dosing Schedules
We defined a primary series as either 2 or 3 doses received before 7 months of age. A booster dose was defined as a dose of PCV or PPV23 received after 9 months of age and after the completion of a primary series. A complete series was defined as the primary series plus any booster doses implemented in a population; examples of this include a 2-dose primary series with or without a booster (2+1, 2+0) or a 3-dose primary series with or without a booster (3+1, 3+0).
Data Analysis
Studies evaluating impact on pneumonia following PCV introduction used a variety of methods; the variety prevented us from performing a formal meta-analysis. Therefore, we conducted descriptive analyses of the amount and variability of the data and of the magnitude of the change in the pneumonia outcomes observed for each dosing schedule type. We also performed subanalyses to evaluate various endpoints related to pneumonia. Studies reporting only qualitative data with no ability to determine magnitude of impact were excluded from analysis.
For observational studies reporting pneumonia incidence over time, we calculated percent change as: (baseline incidence —post-PCV introduction incidence)/baseline incidence. Baseline incidence was defined as the mean of all data points reported before PCV introduction. When annual data on postintroduction incidence were available, we calculated percent change using the data point given for each year reported. When only the average postintroduction incidence rate over a period of years was provided, we calculated percent change from baseline to the reported rate and assigned it to the median year of the date range provided. When possible, incidence rates during the year of introduction were excluded from these calculations. We conducted all analyses using SAS 9.3 (SAS Institute Inc., Cary, NC).
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