Association between opioid use and the development of diverticulitis (Opioids Diverticulitis)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name, other:
  Opioids
• Anatomical Therapeutic Chemical (ATC) code:
  (N02AA) Natural opium alkaloids

  Natural opium alkaloids

  (N02AB) Phenylpiperidine derivatives

  Phenylpiperidine derivatives

  (N02AC) Diphenylpropylamine derivatives

  Diphenylpropylamine derivatives

  (N02AD) Benzomorphan derivatives

  Benzomorphan derivatives

  (N02AE) Oripavine derivatives

  Oripavine derivatives

  (N02AF) Morphinan derivatives

  Morphinan derivatives

  (N02AJ) Opioids in combination with non-opioid analgesics

  Opioids in combination with non-opioid analgesics

  (N02AX) Other opioids

  Other opioids

  (N07BC) Drugs used in opioid dependence

  Drugs used in opioid dependence
• Medical condition to be studied:
  Diverticulitis
• Additional medical condition(s):
  Three indications for the initiation of opioid treatment: 1) post-surgical pain, 2) post-trauma pain, and 3) other pain indications.

Population studied

• Short description of the study population:
  Individuals who had an indication for opioid use (subsequently described) between April 1, 2004, and March 31, 2020, in 5 Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan), the UK, and the US.
• Age groups:
  • 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:
  24.369.137

Study design details

• Study design:
  Feasibility Study; Multicentre retrospective descriptive cohort study; Comparative Safety Study; The comparative safety study was a multicentre retrospective cohort study
• Main study objective:
  The main objective of this multi-centre population-based study is to evaluate whether opioid use is associated with elevated risk of diverticulitis in patients indicated for treatment with opioids.
• Setting:
  Administrative health databases from 5 Canadian provinces (Alberta, British Columbia, Manitoba, ; Ontario, and Saskatchewan), the UK CPRD (Aurum), and the US Merative MarketScan
• Outcomes:
  The risk of diverticulitis will be assessed on the landmark date (see follow-up section below) by an emergency department or inpatient primary discharge diagnosis of diverticulitis. Severe diverticulitis will be defined as an inpatient primary discharge diagnosis of diverticulitis with an accompanying computed tomography (CT) scan. The risks will be assessed within 30, 180, and 730 days.
• Data analysis plan:
  Three indication cohorts for opioid treatment (defined above) between 2004-2020 will be created in each site, with patients allowed into multiple cohorts. Analyses will be conducted using inverse probability of treatment weights and odds weights separately. Patient characteristics and prevalence of opioids use (new use, prevalent use, and non-use) will be described for each indication. Incidence rate ratios and differences, and risk ratios and differences of diverticulitis (defined above) will be estimated among prevalent and non-users of opioids compared with new users. Follow-up will be defined using both an intention-to-treat and an as-treated approach (with inverse probability of censoring weights). Subgroups analyses (if feasible) by sex, age, and sub-class of surgical indication will be conducted. Patients with prevalent or new use of opioid maintenance therapy will be excluded in a sensitivity analysis. Site-specific results will be pooled using random effects meta-analysis.