RISK OF AGRANULOCYTOSIS ASSOCIATED WITH THE USE OF DRUGS

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (N02) ANALGESICS

  ANALGESICS
• Medical condition to be studied:
  Agranulocytosis

Population studied

• Age groups:
  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:
  1200

Study design details

• Main study objective:
  The main objective is to estimate the risk of Agranulocytosis associated to several drugs.
• Outcomes:
  Odds ratios are calculated after controlling for confounding by applying a multiple logistic regression model, including potential known confounders and drug terms. Case-fatality rate for drugs showing odds ratio values significantly higher than one, population attributable risks are calculated from the odds ratio.
• Data analysis plan:
  The analysis is performed with an unconditional and conditional multiple logistic regression model.For increasing statistical power for risk estimation associated with drugs having a low prevalence of use, the analysis is done with all the cases for which information on drug exposures is available, and their respective controls of agranulocytosis. The model included sex, age, and interviewer as additional terms. Drug exposures are considered in different ways. The main analysis refers to any exposure during the week before the index day, this definition of exposure is decided after taking into account that for most of the cases of agranulocytosis, the time elapsed from injury of the bone marrow or of peripheral neutrophils to the appearance of the initial symptoms of infection is usually less than 7 days. The following 2 additional confirmatory analyses are performed: one, with the aim of exploring possible information bias, and the other, to evaluate protopathic bias.