Study type

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness
Drug utilisation
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

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

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

24369137
Study design details

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.

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.
Documents
Study report