DARWIN EU® Use of take-home naloxone for opioid overdose treatment

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name, other:
  naloxone Nasal Spray; naloxone Prefilled Syringe ; naloxone Auto-Injector
• Study drug International non-proprietary name (INN) or common name:
  NALOXONE HYDROCHLORIDE DIHYDRATE
• Anatomical Therapeutic Chemical (ATC) code:
  (V03AB15) naloxone

  naloxone
• Additional medical condition(s):
  Opioid-induced mood disorder due to opioid abuse, Intravenous nondependent opioid abuse, Nondependent opioid abuse (continuous and episodic), Opioid abuse, Nondependent opioid abuse, Opioid-induced mood disorder due to opioid dependence, Opioid dependence with current use, Opioid analgesic dependence, Opioid dependence, Episodic opioid dependence, Continuous opioid dependence, Combined opioid with other drug dependence, Fentanyl dependence, Methadone dependence, Opium dependence, Heroin dependence, Morphine dependence

Population studied

• Short description of the study population:
  Population-level utilization of THN: All individuals present in the database in the period between 01/01/2017 and 31/12/2022 will be included in the analysis after 365 days of database history. Therefore, children aged <1year will be excluded. ; Patient-level THN utilization: All “new” users of THN in the period between 01/01/2017 and 31/12/2022, with “new” users being defined as all people with a prescription THN within the study period, with at least 365 days of availability prior to the date of their THN prescription and no prescription of THN in the last 7 days (180 days for sensitivity analysis). Therefore, the same person can be a “new” user multiple times during the study period.
• Age groups:
  • 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:
  17.700.000

Study design details

• Study design:
  - Population level cohort study; - New drug user cohort study
• Main study objective:
  (i) To investigate the incidence and prevalence of THN use in (1) the general population and (2) among people with a recorded history of opioid use disorder during the study period 2017-2022. ; (ii) To provide summary baseline characteristics of “new” THN users ; (iii) To study the use of THN in ”new” users;
• Data analysis plan:
  Population-level THN use: Annual period prevalence of THN use and annual incidence rates per 100,000 person years in (1) the general population and (2) among people with a recorded history of opioid use disorder (OUD). Patient-level THN use: Summary baseline characteristics of “new” users incl. demographics and history of opioid use, overdose will be conducted. Index date will be the date of the respective prescription of THN for each person. Number of THN prescriptions/packages per “new” user at index date will be summarised and mean (SD), median, p25 and p75 provided. For all analyses a minimum cell count of 5 will be used when reporting results, with any smaller counts obscured.
• Summary results:
  Our study assessing the use of take-home naloxone for opioid overdose treatment in 4 primary care/outpatient specialised care databases from 4 European countries showed very few THN prescriptions captured in these settings. No prescriptions were seen for SIDIAP and IQVIA LPD Belgium. ; With this, our study may provide useful information for future studies on take-home naloxone: based on our estimates of incompleteness and lack of generalisability, future researchers should consider the very specific regional/national distribution pathways, i.e. through specialised support services and facilities, for take-home naloxone in the context of public health programs to prevent opioid overdoses. ; Limited prescriptions of THN nasal spray were recorded in the selected primary care or specialized outpatient care practices databases to quantify and characterise THN users. This suggests that take-home naloxone preparations are mostly dispensed through specialised support services and community-based facilities that take part in regional or national take-home naloxone programs and, as a consequence, are not routinely captured in the available and selected databases for this study. ; This study identified important elements to consider on prescribed product information to improve the feasibility assessment process for future DARWIN EU® studies. This includes the process for generating feasibility counts, which now utilises feasibility codes for concept sets, such as groups of relevant products with a certain route of administration, instead of an ingredient-based search only. The use of “DrugExposureDiagnostics” R package, which has been developed specifically for DARWIN EU Drug utilisation studies, will be expanded to adopt these changes. Furthermore, it highlights also a potential area for improvement in data collection and/or linkage to capture more broadly data from diverse care settings, that may be relevant to real world data sources in general.