Comparing the Estimated Risk of Hip Fracture Among Subjects Exposed to Tramadol as Compared to Subjects Exposed to Codeine (Tramadol vs Codeine)

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:
  Cohort

  Other
• Non-interventional study design, other:
  Retrospective, observational, comparative

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  CODEINE

  TRAMADOL

Population studied

• Short description of the study population:
  The study used two variants of the target (tramadol) and comparator (codeine) cohorts among 50-89-year-olds with 365 days of continuous observable time prior to the index date. The first cohort variants (T1, C1) excluded subjects who had been exposed to tramadol, codeine, or other opioids within 365 days prior to the index date, hip fracture, cancer, or opioid abuse diagnoses. The second cohort variants (T2, C2) aimed to make the target and comparator cohorts more comparable by excluding subjects diagnosed with cough or cold within 30 days of initial exposure to the opioids of interest and those prescribed cold or cough medications, antibiotics, or antihistamines within 30 days.
• 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:
  Frail population
• Estimated number of subjects:
  1000000

Study design details

• Main study objective:
  Does exposure to tramadol have a different risk of experiencing hip fracture within 1 year, relative to codeine?
• Outcomes:
  Hip fracture
• Data analysis plan:
  This study will follow a retrospective, observational, comparative cohort design . The target cohort is new users of tramadol, the comparator cohort are new users of codeine, and the outcome hip fracture. A Cox proportional hazards regression model will be used to model the time to the first outcome occurrence for the target group relative to the comparator group while accounting for the propensity score (PS) matching. Estimates of risk will be generated as the empirically calibrated hazard ratios (HR), 95% confidence intervals (CI), and p-values. This will be done across four observational datasets.

Documents

Study publications

Herrett E, Gallagher AM, Bhaskaran K, Forbes H, Mathur R, Van Staa T, Smeeth L…

Voss EA, Makadia R, Matcho A, Ma Q, Knoll C, Schuemie M, DeFalco FJ, Londhe A, …

Voss EA, Ma Q, Ryan PB. The impact of standardizing the definition of visits on…