Risk of cardiac valve disorders associated with the use of biphosphonates (Cardiac valve disorders and biphosphonate use)

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 data collection

Non-interventional study

• Non-interventional study design:
  Case-control

  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (M05BA) Bisphosphonates
• Medical condition to be studied:
  Cardiac valve disease

Population studied

• Short description of the study population:
  Patients treated with bisphosphonates who are registered in the databases participating in the study. All the subjects of any age with at least one year of data available in the database were included in the study.
• Age groups:
  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  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:
  27000000

Study design details

• Main study objective:
  The primary objective of this study is to confirm, or refute, the existence of a statistical association of cardiac valve disorders (all types of disorders, confirmed by echocardiography, cardiac catheterisation, or other imaging modality) and use of bisphosphonate (for all indications), and eventually to identify effect modifiers.
• Outcomes:
  Occurrence of any cardiac valve disorder
• Data analysis plan:
  Through data mining techniques any association of individual bisphosphonates and each outcome definition will be explored and quantified. Various statistical methods have previously been evaluated for this purpose and in this study a combination of the best performing methods, enumerated below, will be applied to data pooled from all six databases. a. Incidence Rate Ratio (IRR) is calculated as the ratio between incidence rate during exposure to the drug compared to a background incidence rate. A Mantel-Haenszel test is used to test the differences between the incidence rates, typically correcting for age and sex. b. Longitudinal Gamma Poisson Shrinker (LGPS) is an adaptation of the GPS method, developed for use in spontaneous reporting databases, to longitudinal data. It applies Bayesian shrinkage to the IRR.c. Automated Matched Case Control Method. For every potential case identified, a predefined number of controls will be matched to the same age, sex, index date.

Documents

Study results

Executive Summary