Prescription Drug Safety and Effectiveness in Multiple Sclerosis

NCT ID: NCT04472975

Last Updated: 2024-05-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 35000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 1996-01-01
• Study Completion Date: 2018-03-31

Brief Summary

The goal of our research is to find out how safe and effective the drugs used to treat multiple sclerosis (MS) are when used in the everyday, real world. To achieve these study goals, we have two main study Themes. The first Theme focuses on how effective the MS drugs are. We will examine whether the MS drugs can extend life expectancy or prolong a person's ability to stay mobile and walk. We will also look at whether the MS drugs have a beneficial effect on reducing the number of times a person with MS is admitted to a hospital or visits a physician. The second Theme focuses on side effects, including whether the MS drugs are associated with harmful effects, such as cancer, stroke or depression. We will be able to compare the different MS drugs to each other. Also, we will see if men and women or people of different ages and with other illnesses (such as having both MS and diabetes) respond to the MS drugs differently. Our findings will help people with MS and their physicians when trying to make decisions as to which MS drug might be best for them.

Detailed Description

Study population:

A validated case definition of multiple sclerosis (MS) will be applied to the health administrative data to identify all MS patients in 5 Canadian provinces (British Columbia, Manitoba, Nova Scotia, Saskatchewan and Alberta; Studies 1,2,4-6). Developed in Manitoba, the positive predictive value was 80.5% and negative predictive value (NPV) was 75.5% among a population of persons with ≥1 claim for any demyelinating disease. The NPV would be >99% at the general population level where more than 98% of individuals have no claims for demyelinating disease. The algorithm has been successfully applied in British Columbia, Nova Scotia and Saskatchewan.

When MS-specific clinical data are used (British Columbia, Manitoba, Nova Scotia; Study 3), the diagnosis is neurologist confirmed, according to the prevailing international criteria.

Study period:

The earliest study start is Jan/1996 (the 1st full year that DMDs were available and the first year of available administrative and DMD-related data), and the latest study end is March 31, 2018; this represents >2 decades of drug and patient-related follow-up.

Study entry:

Most recent of 1-Jan-1996, an individual's 18th birthday, date of 1st MS-related claim or date of 1st MS clinic visit (when clinical data are accessed [Study 3]).

Study end:

Earliest of death, emigration from the respective province, last MS clinic visit (when clinical data are accessed [Study 3]), or 31-December-2017 (British Columbia, Manitoba, Nova Scotia, Alberta) or 31-March-2018 (Saskatchewan).

DMD exposure:

DMD use, as identified using prescription data. An individual's exposure status can change over time and will be dynamically classified as: 1) no DMD, 2) any DMD, then by generation: 2a) any 1st or 2b) 2nd generation DMD. When possible, the individual drug classes will be explored (beta-interferon [as one class], glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, alemtuzumab).

Time perspective:

Analyses of prospectively recorded health administrative, prescription and clinical data.

Conditions

Multiple Sclerosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Multiple sclerosis (MS) cohort

Individuals with multiple sclerosis without any exposure to disease-mofidying drugs (DMDs) and with exposure to one or more DMDs.

Exposure to one or more disease-modifying drug(s)(DMDs) used to treat MS

Intervention Type: DRUG

Individuals with MS exposed to one or more DMDs (beta-interferon, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, alemtuzumab, daclizumab or ocrelizumab; regardless of dose, frequency or duration of treatment) between 1st January 1996 and 31st March 2018 in five Canadian provinces.

Interventions

Exposure to one or more disease-modifying drug(s)(DMDs) used to treat MS

Individuals with MS exposed to one or more DMDs (beta-interferon, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, alemtuzumab, daclizumab or ocrelizumab; regardless of dose, frequency or duration of treatment) between 1st January 1996 and 31st March 2018 in five Canadian provinces.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• All MS patients (Studies 1, 2, 4-6) who have resided in one of the 5 Canadian provinces (British Columbia, Manitoba, Nova Scotia, Saskatchewan or Alberta) over the study period as identified using a validated case definition of MS that will be applied to health administrative data (≥ 3 records related to MS coded during physician or hospital visits, or prescription filled for a MS-specific DMDs).
• Subjects require 1 year of residency in a province before study entry to enable sufficient data to facilitate covariate creation, e.g. comorbidity, and to identify those with prior DMD use.
• All adults who visited a MS clinic in British Columbia, Manitoba or Nova Scotia (Study 3), were diagnosed with MS and had a relapsing-onset disease course and at least one EDSS score of 6.5 or less, recorded on or after: January 1st 1996 (British Columbia) or April 1st 1996 (Manitoba) or January 1st 1998 (Nova Scotia).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Manitoba

OTHER

Sponsor Role: collaborator

Dalhousie University

OTHER

Sponsor Role: collaborator

University of Saskatchewan

OTHER

Sponsor Role: collaborator

Alberta Health services

OTHER

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: collaborator

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Helen Tremlett

Professor, Canada Research Chair in Neuroepidemiology and Multiple Sclerosis

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Helen Tremlett, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

References

Ng HS, Zhu F, Kingwell E, Zhao Y, Yao S, Ekuma O, Svenson LW, Evans C, Fisk JD, Marrie RA, Tremlett H. Disease-modifying drugs for multiple sclerosis and subsequent health service use. Mult Scler. 2022 Apr;28(4):583-596. doi: 10.1177/13524585211063403. Epub 2021 Dec 24.

Reference Type: DERIVED

PMID: 34949130 (View on PubMed)

Other Identifiers

CIHR PJT-156363

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CIHR FDN-159934

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

H18--00407

Identifier Type: -

Identifier Source: org_study_id