Data design and source
A retrospective cohort design and data from the Health Risk Institute (HRI) Research Database spanning 2008–2012 were employed. The HRI Database comprises medical and drug claims from an age and gender representative sample of 3.4 million persons covered by the statutory health care system in Germany, approximately 4 % of the total population. The HRI Scientific Board approved our study and granted access to the HRI Research Database.
Data available from each medical claim include date/quarter of service, place of service, diagnoses (International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification [ICD-10-GM]), procedures performed/services rendered, and quantity of services. Data available for each drug claim include the agent dispensed (as set forth by the Anatomical Therapeutic Chemical [ATC] System), dispensing/prescription date, and quantity dispensed. Medical and drug claims also include amounts paid (i.e., reimbursed) to providers by health insurers. Selected demographic and eligibility information (including age/year of birth, sex, dates of enrollment) also is available for persons in the HRI Database. All data can be arrayed to provide a detailed chronology of medical and pharmacy series used by each insured member over time.
Insurance benefits extend to all healthcare services. The HRI Database does not include data on clinical parameters (e.g., lab results), quality of life, or markers of disease severity because health insurers in Germany are prohibited by federal law from having such information. All patient-level data in the HRI Research Database are de-identified to comply with German data protection regulations. Use of the study database for health services research is therefore fully compliant with German federal law and, accordingly, IRB/ethical approval was not needed.
The study population comprised persons who were enrolled in a health insurer represented in the HRI Database on January 1, 2009. Persons who were not continuously eligible for health insurance benefits for at least one year prior to January 1, 2009 were excluded from the study population; less than 0.5 % of the population from the HRI Database was excluded due to this criterion. Infants <12 months of age as of this date were not subject to this exclusionary criterion.
Study subjects were stratified based on their age (<5, 5–17, 18–49, 50–59, and ≥60 years) and risk profile (“at-risk”, “high-risk”, and “healthy”). Risk profiles were defined based on the presence of medical conditions that are indications for pneumococcal vaccination among children and adults including alcoholism, asthma, chronic heart disease, chronic liver disease, chronic lung disease, chronic renal failure, cochlear implant, Crohn’s disease, diabetes, Down’s syndrome, functional/anatomic asplenia, HIV, immunosuppressant therapy, short gestation/low birthweight, smoking, as well as those medical conditions hypothesized to be associated with increased risk including neuromuscular/seizure disorders, rheumatoid arthritis, and systemic lupus erythematosis [13–16]. The list of medical conditions was based on recommendations for vaccination set forth by STIKO and/or ACIP, as well as other conditions previously reported to confer an increased risk of pneumococcal disease.
Immunocompetent persons with ≥1 chronic medical condition were classified as at-risk; immunocompromised/immunosuppressed persons and those with a cochlear implant were classified as high-risk. At-risk and high-risk were mutually exclusive categories and thus, for example, persons considered immunosuppressed due to cancer treatment were included in the high-risk category only, even if they also had an at-risk condition. Persons without evidence of at-risk or high-risk conditions were classified as healthy. At-risk and high-risk medical conditions were ascertained using ICD-10-GM diagnosis codes recorded any time prior to the beginning of the 2009 calendar year. Operational algorithms employed to identify at-risk and high-risk conditions are available in Additional file 1: Table S1 and Additional file 2: Table S2, respectively, of the online supplement.
Episodes of all-cause pneumonia (i.e., all clinical cases caused by all known and unknown pathogens, including S. pneumoniae) were identified during the four-year period beginning on January 1, 2009 and ending on December 31, 2012 or the date of health insurer disenrollment, whichever occurred first. Episodes were identified using operational algorithms based on corresponding diagnosis codes (ICD-10-GM) in the principal or secondary position, procedure codes for inpatient care (Operationen- und Prozedurenschlüssel [OPS]), and ATC drug codes, as set forth in the online supplement (Additional file 3: Table S3); cases that were invasive (i.e., bacteremic) in nature were excluded from consideration. Multiple episodes of all-cause pneumonia for a given patient were included as independent events if they were separated by ≥90 days.
Incidence rates of all-cause pneumonia episodes were estimated for children and adults within each age group by risk profile as well as individual medical condition, and were expressed per 100,000 person-years. Rate ratios for disease episodes among persons with at-risk and high-risk conditions, respectively—overall and by individual medical condition—versus their age-stratified healthy counterparts were estimated using Poisson regression (SAS v 9.3). Rates of disease and corresponding rate ratios (vs. healthy counterparts) also were calculated for at-risk persons by the number of at-risk conditions.