Multiple SclerosisDRUMSNCT04472975
Prescription Drug Safety and Effectiveness in Multiple Sclerosis
An observational study of Multiple Sclerosis, run by University of British Columbia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Exposure to one or more disease-modifying drug(s)(DMDs) used to treat MS
- How many people
- 35,000 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 1996to 31 Mar 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: A MS cohort study (Studies 1, 2, 4-6) will be identified using a validated case definition of MS that will be applied to the whole-population linked administrative health data in five Canadian provinces spanning from west to east coast: British Columbia (BC; population 4.65 million [2016]), Alberta (AB; 4.07 million population [2016]), Saskatchewan (SK; population 1.10 million [2016]), Manitoba (MB; population 1.28 million [2016]) and Nova Scotia (NS; population 924,000 [2016]). 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. Within each province, we anticipate finding virtually the whole population of people living with MS via the administrative data, and, in the clinical data, ≈60-80% or 100% of those seeking DMDs (the MS clinics are the sole prescribers of the DMDs).
Who may be able to join
- 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).
Who cannot join
None listed.
About this study
Official title: Disease-modifying Drug Safety and Effectiveness in Multiple Sclerosis [DRUMS]
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.
Read the 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
- Being tested
- Exposure to one or more disease-modifying drug(s)(DMDs) used to treat MS
- Keywords
- disease-modifying drugs, health administrative data, population-based, Canada, cohort studies
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure to one or more disease-modifying drug(s)(DMDs) used to treat MSDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Multiple sclerosis (MS) cohort | Individuals with multiple sclerosis without any exposure to disease-mofidying drugs (DMDs) and with exposure to one or more DMDs. Receives: Drug: Exposure to one or more disease-modifying drug(s)(DMDs) used to treat MS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study 1: All-cause hospitalizations
The outcome (all-cause hospitalizations) will be derived from the comprehensive hospital data, excluding pregnancy-related events, in 5 Canadian provinces (British Columbia, Manitoba, Nova Scotia, Saskatchewan and Alberta).
Measured: As recurrent events from study entry to study end, up to 22 years.
Study 2: All-cause mortality
The outcome (all-cause mortality) will be derived from the province-wide death data (e.g., Vital Statistics or the equivalent) in 5 Canadian provinces (British Columbia, Manitoba, Nova Scotia, Saskatchewan and Alberta).
Measured: Measured using Cox proportional hazards models (time from study entry to death), up to 22 years.
Study 3: Change in disability (Expanded Disability Status Scale [EDSS]) over time
The outcomes (change in EDSS) will be derived from the MS clinical data in 3 Canadian provinces (British Columbia, Manitoba and Nova Scotia).
Measured: Assessed using mixed effects model from study entry to study end, up to 22 years.
Secondary outcomes (6)
Study 1: Physician consultation rates (overall and by physician specialty)
The outcome (physician consultation) will be derived from the physician data, excluding pregnancy-related events, in 5 Canadian provinces (British Columbia, Manitoba, Nova Scotia, Saskatchewan and Alberta).
Measured: Overall numbers of physician consultations will be measured from study entry to study end, up to 22 years of follow-up.
Study 3: MS disability, measured using the Expanded Disability Status Scale (EDSS) and assessed as time to sustained EDSS 6
The outcome (sustained EDSS 6) will be derived from the MS clinical data in 3 Canadian provinces (British Columbia, Manitoba and Nova Scotia).
Measured: Measured using Cox proportional hazards models (time from study entry to sustained EDSS 6 confirmed after at least 6 months with no subsequent improvement), up to 22 years of follow-up.
Study 3: Sustained EDSS 4
The outcomes (sustained EDSS 4) will be derived from the MS clinical data in 3 Canadian provinces (British Columbia, Manitoba and Nova Scotia).
Measured: Measured using Cox proportional hazards models (time from study entry to sustained EDSS 4), up to 22 years of follow-up.
Study 4: Explore the modifying effects
Effects of sex, age, comorbidity and DMD treatment duration on outcomes (all-cause hospitalizations, physician consultation rates, all-cause mortality, changes in EDSS) will be assessed.
Measured: From study entry to study end, up to 22 years of follow-up.
Study 5: Potential incident adverse events
'Incident' event defined as not present in the year before DMD initiation. The outcomes (incident adverse events) will be identified using physician and hospital claims, coded using International Classification of Diseases [ICD]-9/10 and prescriptions filled (by ATC levels), in 5 Canadian provinces (British Columbia, Manitoba, Nova Scotia, Saskatchewan and Alberta). An additional, data mining, discovery approach will assess the associations between exposure and adverse events using unsupervised machine learning techniques. Cases of PML will be described.
Measured: Time from study entry to the incident adverse event of interest will be assessed using Cox proportional hazards with time-varying DMD exposure, up to 22 years of follow-up.
Study 6: Characteristics associated with risk of adverse events
Examine demographic and clinical characteristics associated with risk of adverse events, including sex, age, comorbidity and DMD treatment duration.
Measured: From study entry to study end, up to 22 years of follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2020
- Study start1 Jan 1996
- Primary completion31 Mar 2018
- Study completion31 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 35,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Manitoba, Dalhousie University, University of Saskatchewan, Alberta Health services, University of Alberta
- Responsible party
- Principal investigator, Helen Tremlett, University of British Columbia
- Investigators
- Helen Tremlett, PhD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04472975
- Sponsor's protocol ID
- H18--00407
- Other IDs
- CIHR PJT-156363, CIHR FDN-159934
- Acronym
- DRUMS
- Status last verified
- May 2024
- First submitted
- 3 Jul 2020
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The data that were used for this study reside on a limited access secure research environment and for legal and ethical reasons, the data cannot leave this secure research environment. However, researchers can apply to access the health administrative data held within each province.
Publications
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.
PubMed 34949130
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Disease-modifying Drug Safety and Effectiveness in Multiple Sclerosis [DRUMS]
- ClinicalTrials.gov ID
- NCT04472975
- Acronym / sponsor ID
- DRUMS / H18--00407
- Conditions
- Multiple Sclerosis
- Keywords
- disease-modifying drugs, health administrative data, population-based, Canada, cohort studies
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 35,000 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- University of Manitoba, Dalhousie University, University of Saskatchewan, Alberta Health services, University of Alberta
- Study start
- 1 Jan 1996 (actual)
- Primary completion
- 31 Mar 2018 (actual)
- Study completion
- 31 Mar 2018 (actual)
- First posted
- 16 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multiple sclerosis (MS) cohort | – | Drug: Exposure to one or more disease-modifying drug(s)(DMDs) used to treat MSIndividuals with multiple sclerosis without any exposure to disease-mofidying drugs (DMDs) and with exposure to one or more DMDs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- A MS cohort study (Studies 1, 2, 4-6) will be identified using a validated case definition of MS that will be applied to the whole-population linked administrative health data in five Canadian provinces spanning from west to east coast: British Columbia (BC; population 4.65 million [2016]), Alberta (AB; 4.07 million population [2016]), Saskatchewan (SK; population 1.10 million [2016]), Manitoba (MB; population 1.28 million [2016]) and Nova Scotia (NS; population 924,000 [2016]). 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. Within each province, we anticipate finding virtually the whole population of people living with MS via the administrative data, and, in the clinical data, ≈60-80% or 100% of those seeking DMDs (the MS clinics are the sole prescribers of the DMDs).
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exposure to one or more disease-modifying drug(s)(DMDs) used to treat MSIndividuals 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. | Drug | Multiple sclerosis (MS) cohort |
Primary outcome
Study 1: All-cause hospitalizations
Time frame: As recurrent events from study entry to study end, up to 22 years.
The outcome (all-cause hospitalizations) will be derived from the comprehensive hospital data, excluding pregnancy-related events, in 5 Canadian provinces (British Columbia, Manitoba, Nova Scotia, Saskatchewan and Alberta).
Study 2: All-cause mortality
Time frame: Measured using Cox proportional hazards models (time from study entry to death), up to 22 years.
The outcome (all-cause mortality) will be derived from the province-wide death data (e.g., Vital Statistics or the equivalent) in 5 Canadian provinces (British Columbia, Manitoba, Nova Scotia, Saskatchewan and Alberta).
Study 3: Change in disability (Expanded Disability Status Scale [EDSS]) over time
Time frame: Assessed using mixed effects model from study entry to study end, up to 22 years.
The outcomes (change in EDSS) will be derived from the MS clinical data in 3 Canadian provinces (British Columbia, Manitoba and Nova Scotia).
6 secondary outcomes
Study 1: Physician consultation rates (overall and by physician specialty)
Time frame: Overall numbers of physician consultations will be measured from study entry to study end, up to 22 years of follow-up.
Study 3: MS disability, measured using the Expanded Disability Status Scale (EDSS) and assessed as time to sustained EDSS 6
Time frame: Measured using Cox proportional hazards models (time from study entry to sustained EDSS 6 confirmed after at least 6 months with no subsequent improvement), up to 22 years of follow-up.
Study 3: Sustained EDSS 4
Time frame: Measured using Cox proportional hazards models (time from study entry to sustained EDSS 4), up to 22 years of follow-up.
Study 4: Explore the modifying effects
Time frame: From study entry to study end, up to 22 years of follow-up.
Study 5: Potential incident adverse events
Time frame: Time from study entry to the incident adverse event of interest will be assessed using Cox proportional hazards with time-varying DMD exposure, up to 22 years of follow-up.
Study 6: Characteristics associated with risk of adverse events
Time frame: From study entry to study end, up to 22 years of follow-up.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Derived from this study: PubMed 34949130Ng 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.
- Individual participant dataSharing planned: No. The data that were used for this study reside on a limited access secure research environment and for legal and ethical reasons, the data cannot leave this secure research environment. However, researchers can apply to access the health administrative data held within each province.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen Tremlett, PhD principal investigator
University of British Columbia
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by University of British Columbia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Study 1: All-cause hospitalizations (time frame: As recurrent events from study entry to study end, up to 22 years.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04472975, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.