A retrospective matched cohort study on the association between herpes zoster vaccination and dementia and mild cognitive impairment using electronic health records (ZOSTER-122 AIML 222419)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Other

  Safety study (incl. comparative)
• If ‘other’, further details on the scope of the study:
  Hypothesis testing
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  SHINGRIX

  ZOSTAVAX

  PNEUMOVAX 23
• Study drug International non-proprietary name (INN) or common name:
  CROTALINE ANTIVENIN, POLYVALENT

  HERPES ZOSTER NOSODE D12

  HERPES ZOSTER VACCINE (RECOMBINANT, ADJUVANTED)
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BK02) zoster, live attenuated

  zoster, live attenuated

  (J07BK03) zoster, purified antigen

  zoster, purified antigen

  (J07AL01) pneumococcus, purified polysaccharides antigen

  pneumococcus, purified polysaccharides antigen
• Medical condition to be studied:
  Herpes zoster

  Dementia

  Cognitive disorder

Population studied

• Short description of the study population:
  Inclusion criteria: ; Ø Electronic health records available in the Optum® EHR. ; Ø Age at exposure >= 50. ; Ø For SHINGRIX, SHINGRIX-2D, ZOSTAVAX, PPSV23, HZ single, HZ multiple, HZ treated with AAT, HZ not treated with AAT, Corticosteroids HIGH, Corticosteroids-LOW: Recorded exposure (see Section “Exposure; definitions”). ; Ø For Not Exposed: Encounter(s) within +/- 3 months of the exposure date of the matched individual.
• Age groups:
  • Adults (46 to < 65 years)
  • Elderly (≥ 65 years)

    • Adults (65 to < 75 years)
    • Adults (75 to < 85 years)
    • Adults (85 years and over)
• Estimated number of subjects:
  10000000

Study design details

• Study design:
  Retrospective, observational, matched-cohort study
• Main study objective:
  To determine if there is an association between either or both ZOSTAVAX and SHINGRIX and dementia primary or mild cognitive impairment (MCI) secondary using the same large scale, US electronic health record (EHR) database.
• Setting:
  The source population consists of more than 100 million individuals with electronic health records available in the Optum® EHR database with start of records in 2007 - including more than 2000 hospitals and 5000 clinics in the United States. The data consists of primarily large integrated delivery networks (IDNs; accounting for ~80% of the data).
• Outcomes:
  Dementia, Vascular dementia, Mild cognitive impairment (MCI), Herpes Zoster
• Data analysis plan:
  Matched cohorts defined by their exposure to various elective adult immunizations and control conditions will be compared in pairwise fashion. For each comparison pair, the following will be reported: ; • Relative risk (RR) between cumulative hazards in the compared cohorts estimated by Nelson-Aalen method at 3- and 5-years post-exposure. ; • Statistical significance test results (p-value) of comparing the cumulative hazard distributions between the compared cohorts at 3- and 5-years post-exposure using Chi2 test accounting for censoring (two-sided, alpha = 0.05). ; • Pre- and post-matching descriptive cohort statistics covering covariates, outcomes and matching factors. ; • Cumulative hazard curves (y-axis: cumulative hazard, x-axis: time) for both comparison groups estimated by Nelson-Aalen including confidence intervals to enable qualitative analysis.