Pan European Multi-Database Bladder Cancer Risk Characterisation Study

Study type

• Study topic:
  Disease /health condition

  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:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  PIOGLITAZONE
• Medical condition to be studied:
  Type 2 diabetes mellitus

Population studied

• Short description of the study population:
  Patients ≥ 40 years with type 2 diabetes mellitus in four European countries: Finland, Netherlands, Sweden, and United Kingdom whose antidiabetic treatment at cohort entry was modified to include pioglitazone or another antidiabetic medication.; Patients with following criteria were included:; • Treatment with any oral antidiabetic drugs at any time in the available medication records.; • Baseline is modified (cohort entry point) to include pioglitazone (exposure group) or another antidiabetic medication (reference group); • Age ≥ 40 years at cohort entry; • At least 12 months of medication database membership during baseline period prior to cohort entry
• Age groups:
  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Type 2 diabetes mellitus patients
• Estimated number of subjects:
  760000

Study design details

• Main study objective:
  To estimate and compare the absolute and relative risk of bladder cancer in patients with type 2 diabetes who are ever exposed to pioglitazone vs. never exposed to pioglitazone.
• Outcomes:
  Date of diagnosis of the first incidence of bladder cancer after the entry into the study cohort. - All cause mortality- Bladder cancer mortality
• Data analysis plan:
  Crude bladder cancer incidence and mortality rates with 95% CI will be estimated for each pioglitazone exposure definition separately within the strata of gender, age, year of cohort entry, duration of disease, medication and disease history. Crude incidence rates for each country will be provided separately. In the propensity score matched cohort analysis HR estimates with 95% CIs for each pioglitazone exposure definition will be estimated using Cox model with a counting process approach which enables the follow-up time of each patient to be split into several periods and thus allows adjustments for relevant baseline and time-dependent covariates in the model specification. Separate analyses of bladder cancer incidence, bladder cancer mortality and all-cause mortality will be performed for each country/dataset. In meta-analysis the pooled data set will be used and analysed using the similar methods as the individual cohort analyses.

Documents

Study results

Korhonen et al_pioglitazone use and bladder cancer risk_BMJ_2016

Study, other information

9433-2013-02-14-ENCePPProcessWithoutSealLetterFinalSigned

ER-9515-Cause_of_Death_Analysis_Protocol-21-April-2016_signed_Korhonen

ER12-9433-Actos-Pooled Analysis Protocol and Statistical Analysis Plan-Appendices 1-6

ER12-9433-Actos-Pooled Analysis Protocol and Statistical Analysis Plan-Appendix 7

ER12-9433-Pan_EU_bladder_cancer_Pooled_Analysis_Protocol_and_Statistical_Analysis_plan - 12-Feb-2014

Study publications

Korhonen P, Heintjes EM, Williams R, Hoti F, Christopher S, Majak M, Bezemer I,…

Korhonen P, Heintjes EM, Williams R, Hoti F, Christopher S, Majak M, Kool-Houwe…

Strongman H, Korhonen P, Williams R, Bahmanyar S, Hoti F, Christopher S, Majak …