Prodromal Multiple Sclerosis: The PrOMS Study.

Project number: 
14-073
Approval date: 
Wednesday, August 6, 2014
Principal Investigator: 
Tremlett,Helen
Institution: 
University of British Columbia (UBC)
Funding Agency: 
National Multiple Sclerosis Society
Datasets requested: 
Medical Services Plan (BC Ministry of Health)
Consolidation registry (Ministry of Health)
PharmaNet
Hospital Separations (BC Ministry of Health)
consolidation - census geocodes
Mental Health (BC Ministry of Health)
MSP Registration & Premium Billing(BC Ministry of Health)
Consolidation - demographic (Ministry of Health)
Deaths (BC Vital Statistics Agency)
Research objective: 

Broad Study Aim:

Our study aims to investigate the period before diagnosis and identify a pre-MS trait, or prodrome.

Broad Study Hypotheses:

Among persons destined to be diagnosed with MS, after adjustment for possible confounders, we hypothesize that prodromal phase I (period before recognized symptoms of MS) will manifest a measurable signature, distinct from the matched general population or diseased (CIS) controls. We anticipate an excess of health services utilization, including physician and hospital visits, and prescriptions filled, with this excess including a significant mental health component.

The prodromal phase II (MS symptom onset to diagnosis) will be marked by an even greater increase in health services utilization when compared to the matched controls.

Patient characteristics will influence findings, with measurable differences between men, women and the MS disease courses (progressive vs. relapsing-onset).

Further Details:

In order to meet our broad study aim, the Specific Objectives are to:

1. Explore health services utilization patterns (hospital admissions, physician visits, emergency room visits, prescription utilization) in the phase I and II MS prodromes, relative to a matched (age, sex, calendar-year and geographical location) general population cohort.
2. Examine health services utilization patterns across the phases, and explore the impact of MS patient characteristics (e.g. progressive vs. relapsing onset) and temporal changes on utilization
3. Access a diseased control cohort - patients with clinically isolated syndrome (CIS) who did not develop MS (CIS-nonMS) - to help further explore the MS prodrome. The CIS cohort includes patients presenting with either optic neuritis or transverse myelitis involvement. Health services utilization will be compared between those who did and did not develop MS and a matched sample of the general population.

Summary approach and hypotheses for the specific objectives:

Our study capitalizes on the unique health system and research networks in Canada, and involves linkage of clinical databases with multiple large population-based databases, creating powerful datasets in four diverse geographical regions. ** Note: this DAR only applies to the BC data. Please see Methodology, DAR Page 15 of 30 for more details**

Among persons destined to be diagnosed with MS, after adjustment for possible confounders, we hypothesize that prodromal phase I will manifest a measurable signature, distinct from the matched general population or diseased (CIS) controls. We anticipate an excess of health services utilization, including physician and hospital visits, and prescriptions filled, with this excess including a significant mental health component. The prodromal phase II (MS symptom onset to diagnosis) will be marked by an even greater increase in health services utilization when compared to the matched controls. Patient characteristics will influence findings, with measurable differences between men, women and the MS disease courses (progressive vs. relapsing-onset).

Publications: 

Journal Publication

  • Högg T, Wijnands JMA, Kingwell E, Zhu F, Lu X, Evans C, Fisk JD, Marrie RA, Zhao Y, Tremlett H. Mining healthcare data for markers of the multiple sclerosis prodrome
    Mult Scler Relat Disord. October 2018; 25: 232–240
  • Bayesian analysis of pair-matched case-control studies subject to outcome misclassification
    Stat Med. 2017 Nov 20;36(26):4196-4213. doi: 10.1002/sim.7427. Epub 2017 Aug 7.
    Högg T1, Petkau J1, Zhao Y2,3, Gustafson P1, Wijnands JM2, Tremlett H2.
  • José M.A. Wijnands, Elaine Kingwell, Feng Zhu, Yinshan Zhao, Tanja Högg, Karen Stadnyk, Okechukwu Ekuma, Xinya Lu, Charity Evans, John D. Fisk, Ruth Ann Marrie, HelenTremlett. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurology 2017. 16:445-451
  • Wijnands JMA, Kingwell E, Zhu F, Zhao Y, Högg T, Stadnyk K, Ekuma O, Lu X, Evans C, Fisk JD, Marrie RA, Tremlett H. Infection-related health care utilization among people with and without multiple sclerosis. Multiple Sclerosis Journal 2016; 1:1-11

Academic thesis or dissertation

Conference abstract/presentation

  • Wijnands JMA, Kingwell E, Zhu F, Zhao Y, Fisk JD, Evans C, Marrie RA, Tremlett H. Infection-related health care utilization among people with and without MS. Multiple Sclerosis Journal Online 2016; 22 (Suppl pp. 88-399)
  • Wijnands JMA, Hoegg T, Zhu F, Kingwell E, Zhao Y, Fisk JD, Evans C, Ekuma O, Carruthers RL, Marrie RA, Tremlett H. Risk of infection-related hospitalizations in people with primary-progressive relative to relapsing-onset multiple sclerosis. Neurology 2016; 86 (Suppl P3.353)

Page last revised: September 2, 2019