REpositioning of Medications IN Dementia (REMIND)

Study type

• Study topic:
  Disease /health condition

  Other
• Study topic, other:
  Geriatric Pharmacoepidemiology
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

  Hypothesis generation (including signal detection)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

  Cohort

Study drug and medical condition

• Medical condition to be studied:
  Dementia

  Dementia Alzheimer's type

Population studied

• Short description of the study population:
  1. Population for the identification of approved medications which may prevent ADRD:; Inclusion criteria:; - CASES: individuals with an incident diagnosis of ADRD in the SNDS between 01 January 2017 and the end of the study period (31 Dec 2023) with at least 10 years history (i.e., minimum 8 years of lag and 2 years for exposure assessment) in the SNDS and aged 40 years and older at the date of ADRD diagnosis. ; - CONTROLS: Controls will be comprised of individuals with no diagnosis of ADRD in the SNDS prior to the date of the matched case’s ADRD diagnosis with at least 10 years of history in the SNDS at inclusion (i.e., the date of ADRD diagnosis of the matched case). ; Exclusion criteria: None.; ; 2. Population for the comparison of each of the identified medications to an active control (Target Trial Emulation): ; Inclusion criteria: ; Individuals initiating a study medication (i.e., intervention or active control) during the enrollment period (between 01 January 2010 and 31 December 2012), diagnosed with the study medication’s indication, aged 40 years and older at the index date (initiation of medication) with at least 5 years history in the SNDS to rule out prevalent ADRD and a potential follow-up of at least 10 years.; Exclusion criteria: ; History of ADRD, previous use of medication of interest.
• Age groups:
  Adult and elderly population (≥18 years)

  Adults (18 to < 65 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Elderly (≥ 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)

Study design details

• Study design:
  Innovative and complementary drug repurposing approaches to identify new targets to prevent ADRD: a pioneering hypothesis-driven approach and an agnostic signal detection approach.; Target trial emulation with a long follow-up to demonstrate prevention.
• Main study objective:
  The overall objective of REMIND is to identify medications which may prevent ADRD. The drugs identified at the first step will be confirmed by TTE in the SNDS. We will explore if medication combinations are inversely associated with ADRD. The expected outcome is the identification of drugs or combination of drugs that prevent ADRD and new avenues of research in ADRD prevention.
• Setting:
  To identify approved medications which may prevent ADRD and to explore if combinations of approved medications are associated with ADRD, an SNDS nested case-control design will be implemented. Cases will be comprised of individuals with incident diagnosis of ADRD between 01 January 2017 and the end of the study period (31 Dec 2023). ; Controls will be comprised of individuals without an ADRD diagnosis during the historic and study periods matched 5:1 to cases according to age (year of birth), sex and region of residence on the date of case diagnosis. ; ; To compare each of the identified medications to an active control to assess if these drugs reduce the incidence of ADRD in individuals > 40 years, a Target Trial Emulation design will be implemented. For each candidate medication identified, an active control with the same indication, but not impacting the Alzheimer’s disease pathway, will be selected. If no active control can be found meeting these criteria, using methods from high-throughput Target Trial Emulation, candidate medications may be assigned a control in the same second level Anatomical Therapeutic Chemical (ATC) classification category (ATC-L2), or, if impossible, at least 10 to 20 random medications other than the study medication.
• Outcomes:
  Alzheimer's disease and related disorders diagnosis
• Data analysis plan:
  Identification of Candidate Medications: descriptive analyses and Machine Learning Methods in matched case-control study. The association of potential candidates used 8 to 10 years before ADRD with ADRD incidence will be studied.; ; Comparative Analyses: descriptive analyses, crude and adjusted HR and cumulative incidence of ADRD will be estimated for each potential candidate (per protocol effect of medications). Sensitivity analyses will include an intent-to-treat analysis (without censoring when a medication is discontinued or switched), an alternative definition of outcome onset (we will assume that the true date of ADRD onset is 6, 12, and 24 months before the algorithm diagnosis date), and an alternative definition of ADRD (using an algorithm currently under development).