Prescription Drug Safety and Effectiveness in Multiple Sclerosis [DRUMS]: a population-based, multi-province platform for comprehensive pharmacovigilance

Project number: 
18-120
Approval date: 
Friday, September 14, 2018
Principal Investigator: 
Tremlett,Helen
Institution: 
University of British Columbia (UBC)
Funding Agency: 
Canadian Institutes of Health Research(CIHR)
Datasets requested: 
Citizenship and Immigration Canada (CIC) Permanent Residents
Deaths (BC Vital Statistics Agency)
PharmaNet
Consolidation file (BC Ministry of Health)
Consolidation - demographic (Ministry of Health)
consolidation - census geocodes
Hospital Separations (BC Ministry of Health)
Medical Services Plan (BC Ministry of Health)
Research objective: 

Aim 1. Investigate the relationship between Disease Modifying Drug (DMD) exposure and health service use.
Aim 2. Assess the relationship between DMD exposure and all-cause mortality.
Aim 3. Examine the relationship between DMD exposure and MS specific clinical outcomes, as measured using the Expanded Disability Status Scale (EDSS) and onset of secondary progression (SP).
Aim 4. Explore the effects of sex, age, comorbidity and treatment duration on Aim 1-3 outcomes.
Aim 5. Provide a comprehensive assessment of potential adverse events associated with the DMDs.
Aim 6. Examine characteristics associated with risk of adverse events, including sex, age, comorbidity, and duration and timing of DMD exposure

Hypotheses:
DMDs will be associated with a reduced risk of hospital, physician visits, and all-cause-mortality and with delayed disability progression relative to no DMD exposure. However, the magnitude of effect will differ by DMD;e.g., relative to the 1st generation DMDs (beta-interferon [IFN], glatiramer acetate), the 2nd generation (e.g., natalizumab, fingolimod) will be associated with a reduced risk of hospital visits and with disability delay.

Relative exposure to a 1st generation DMD (IFN, glatiramer acetate) will not alter the risk of cancer or overall infections, relative to no DMD. However, IFN will be associated with a higher risk (relative to no DMD or glatiramer acetate) of: stroke, migraine, and depression, but a reduced risk of specific infections (e.g., bronchitis) thus extending our prior work in BC primarily focused on IFN. Further, we expect the 2nd generation DMDs to be associated with a higher risk of infections, cardiac events, and cancer relative to no DMD or a 1st generation DMD. The magnitude of risk for these adverse events will vary by DMD, and treatment duration/ timing, and will be modified by sex, age, but not by (most) comorbidities (Aim 6).


Page last revised: December 5, 2018