Study type

Study topic

Human medicinal product

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Case-control
Cohort
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(A02BC01) omeprazole
omeprazole
(A02BC02) pantoprazole
pantoprazole
(A02BC03) lansoprazole
lansoprazole
(A02BC04) rabeprazole
rabeprazole
(A02BC05) esomeprazole
esomeprazole
(A02BC06) dexlansoprazole
dexlansoprazole
(A02BC07) dexrabeprazole
dexrabeprazole
Population studied

Short description of the study population

All individuals aged 40 years or older with a minimum of two consecutive years of insurance records with the Allgemeine Ortskrankenkasse AOK Bayern (Germany) between 2008 and 2018 and with the Kassenärztliche Vereinigung Bayerns (Association of Statutory Health Insurance Physicians in Bayern, KVB (Germany), between 2010 and 2018.

Age groups

Adults (18 to < 46 years)
Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Estimated number of subjects

6100000
Study design details

Main study objective

This population-based observational study will investigate whether the long-term use of proton pump inhibitors (PPIs) increases the risk of dementia. The additional study question is the risk of dementia related to different time intervals between PPI exposure and incidence of dementia, and the doseresponse relationship between PPI use and incidence of dementia.

Outcomes

1) The risk of dementia in PPI initiators with two comparator groups:-PPI-nonusers (all PPI-noninitiators among all eligible individuals)- Active comparator users (initiators of an H2RA A02BA, prescribed for a similarindication)2) The dose-response relationship between PPI use and the incidence ofdementia. 1) The risk of dementia among former, recent and current heavy PPI users2) The risk of dementia by active component of PPI.

Data analysis plan

We plan two different study designs and aim to transfer methodological strategies from clinical studies to our data in order to avoid bias that typically arises in observational studies.This approach is called “target trial emulation” and has been proposed in recent studies. Thus, in the cohort study, an intention-to-treat (ITT) analysis will be conducted, and an as-treated analysis will be performed using dose-response modeling. Cohort studies conducted within computerized big databases such as our claims data can be so large that they are technically unmeasurable for data analysis and thus using sampling designs within the cohort is unavoidable. Therefore, we also plan a nested case-control study as a secondary design to analyze the data based on sampling within the cohort as a more accurate reflection of the underlying cohorts.