Detection of therapeutic cascades associated with gabapentinoids and benzodiazepines in adults over 65 years old in Spain using BIFAP through prescription sequence symmetry analysis (GABALOOP)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Drug utilisation

  Safety study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  PREGABALIN
• Study drug International non-proprietary name (INN) or common name:
  PREGABALIN
• Anatomical Therapeutic Chemical (ATC) code:
  (C03AA) Thiazides, plain

  Thiazides, plain

  (C03BA) Sulfonamides, plain

  Sulfonamides, plain

  (C03DA) Aldosterone antagonists

  Aldosterone antagonists

  (C03EA) Low-ceiling diuretics and potassium-sparing agents

  Low-ceiling diuretics and potassium-sparing agents

  (N02BF02) pregabalin

  pregabalin

  (N03A) ANTIEPILEPTICS

  ANTIEPILEPTICS

  (N05A) ANTIPSYCHOTICS

  ANTIPSYCHOTICS

  (N05AX) Other antipsychotics

  Other antipsychotics

  (N05B) ANXIOLYTICS

  ANXIOLYTICS

  (N05C) HYPNOTICS AND SEDATIVES

  HYPNOTICS AND SEDATIVES

  (N07CA) Antivertigo preparations

  Antivertigo preparations

Population studied

• Age groups:
  • Adult and elderly population (≥18 years)

    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  20000

Study design details

• Study design:
  A retrospective, multicenter, longitudinal study using Symmetrical Prescription Sequence Analysis (ASSP).
• Main study objective:
  The objective of this study is to estimate the crude and adjusted rates of sequential prescription combinations of diuretics after gabapentinoids (GABA-DA) and antivertiginous drugs after benzodiazepines (BZD-AV) in the Spanish population over 65 years old with polypharmacy, compared to the rest of the population included in BIFAP.
• Setting:
  All patients with more than 360 days of continuous inclusion in the BIFAP registry prior to the first prescription date of the drug classified as exposure (Appendix I) will be included. This date will determine the cohort entry date, and patients must have at least 180 days of follow-up after this date and remain in the database from the cohort entry date. A drug-free period of 180 days prior to the cohort entry date will be required. The result/event drug will be accepted if initiated within 90 days before or after the cohort entry date. Patients prescribed both the exposure and result drugs simultaneously on the same day will be excluded.
• Comparators:
  Benzodiaceipnes-Antivertiginous drugs
• Outcomes:
  Prescription Cascade
• Data analysis plan:
  The sociodemographic and clinical characteristics of the patients will be described using the mean and standard deviation for normal distributions (or median and range if skewed or non-normal) and by frequency and percentage for categorical variables.; For the symmetrical prescription sequence analysis (ASSP), the sequence ratio, which measures the asymmetry of two specific sequences, will be calculated. This requires identifying new users of both drugs. This analysis was introduced by Petri in 1998 as a rapid cohort crossover method to detect drug-related safety events. It will be calculated by dividing the number of people for whom the event drug was initiated after the exposure drug by the number of people for whom the exposure drug was prescribed after the event drug. Calculated weekly throughout the year, a symmetrical pattern in the distribution of event drug initiation before and after the start of an exposure drug would be expected in the absence of an association. If the event is a very small proportion, the association may be attenuated; therefore, the entire accessible Spanish population is also studied. To minimize the effect of a trend change in the prescription of any of the drugs (gabapentinoids and benzodiazepines, which have increased in recent years), a null effect sequence ratio will be calculated for the background prescription rate of the medications, and adjusted rates will be compared with the population over 65 years old, where a higher risk of diuretic prescription compared to the rest has been observed in other studies (polypharmacy patients <65 years old and non-polypharmacy patients of any age).; To study the factors associated with presenting a therapeutic cascade , a mixed-effects multilevel logistic regression model will be adjusted, using the anonymized physician as a random effect, assuming the physician as the main prescriber, and adjusted for the rest of the first-level variables as fixed effects (independent variables).