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RESEARCH PAPER
Relative mortality and survival in multiple sclerosis:
findings from British Columbia, Canada
E Kingwell,
1
M van der Kop,
1
Y Zhao,
1
A Shirani,
1
F Zhu,
2
J Oger,
1,3
H Tremlett
1
ABSTRACT
Objective To examine mortality and factors associated
with survival in a population based multiple sclerosis
(MS) cohort.
Methods Clinical and demographic data of MS patients
registered with the British Columbia MS clinics
(1980e2004) were linked to provincial death data, and
patients were followed until death, emigration or study
end (31 December 2007). Absolute survival and the
influence of patient characteristics (sex, disease course
(primary progressive (PPMS) vs relapsing onset (R-MS))
and onset age) were estimated by KaplaneMeier
analyses (from birth and disease onset). Mortality
relative to the general population was examined using
standardised mortality ratios. Excess mortality associated
with patient characteristics and time period of cohort
entry was assessed by relative survival modelling.
Results Of 6917 patients, 1025 died. Median survival
age was 78.6 years (95% CI 77.5 to 79.7) for women and
74.3 years (95% CI 73.1 to 75.4) for men. Survival from
onset was longer for R-MS (49.7 years; 95% CI 47.9 to
51.5) than for PPMS (32.5 years; 95% CI 29.5 to 35.7);
however, survival age was similar. The overall
standardised mortality ratios was 2.89 (95% CI 2.71
to 3.07), and patients survived approximately 6 years less
than expected, relative to the general population. PPMS
had a higher relative mortality risk compared with R-MS
(relative mortality ratio (RMR) 1.52; 95% CI 1.30 to 1.80).
Women with PPMS had a relative survival disadvantage
compared with men with PPMS (RMR 1.55; 95% CI 1.19
to 2.01). Relative survival within 10 years of cohort entry
was similar between time periods.
Conclusions Some of the longest MS survival times are
reported here but the risk of death was still greater than
in the age, sex and calendar year matched general
population. No evidence of increased survival over time
was found when improved survival in the general
population was taken into consideration.
INTRODUCTION
Multiple sclerosis (MS) is thought to reduce life
expectancy although findings have varied between
studies; estimates of average life expectancy have
ranged from around 30 to 40 years from onset.
1e10
Comparisons of all cause mortality with the
general population indicate a two to three times
greater risk of mortality associated with MS in
Europe
347e911
and North America.
512
Findings as
to whether MS survival is improving over time
have been conflicting.
34713
The study of mortality and survival with MS is
highly relevant to patients, their families and
healthcare providers, and is important for health
and resource planning. Clues to the underlying
aetiology of the disease may be gained from a better
understanding of survival and from the identifica-
tion of risk factors that contribute to improved
survival. Furthermore, a number of studies are now
examining the impact of immunomodulatory drug
treatments on mortality in MS; suitable survival
data from appropriate geographical regions are
needed for comparison. Finally, there is conflicting
evidence surrounding predictors of survival that
needs to be resolved. Although most studies report
a survival advantage for younger compared with
older onset MS patients,
2 5e71014
findings
regarding the influence of sex and disease course
have been mixed.
4e79e11 13e16
We assessed absolute survival in a large Canadian
MS cohort in British Columbia (BC) and the
influence of sex, disease course at onset (primary
progressive (PPMS) vs relapsing onset (R-MS)) and
age at MS onset on survival. We also examined
survival relative to the general population and
estimated the excess hazard associated with sex,
disease course, age at onset and time period of first
clinic visit.
METHODS
The cohort and data sources
The BC MS database was established in 1980 and
collects information on MS patients seen at the
four MS clinics in BC
17 18
; these clinics remained
the only source of MS specialist care in the province
until 2005. Clinical information including date of
symptom onset and disease course was prospec-
tively documented by clinic neurologists during
visits and entered into the database. The cohort
included all patients in the BC MS database who
first visited a BC MS clinic between 1 August 1980
and 31 December 2004 and were diagnosed with
definite or probable MS by Poser criteria.
19
The BC
Vital Statistics Agency captures more than 99% of
deaths in BC. Between 1980 and 1985, the Agency
directly informed the BC MS clinics of clinic
patient deaths.
12
Deaths that occurred between
1986 and 2007 were captured by linkage of the BC
MS cohort to BC Vital Statistics data. Patients were
linked at the individual level by their personal
health number, a lifelong unique number assigned
under BC’s mandatory universal healthcare plan.
Names and birth dates were used to confirm
linkage accuracy. Once data were linked, all
personal identifying information was removed.
To confirm residence in BC over the course of the
study, the MS cohort was linked with the BC
Ministry of Health Registry and Premium Billing
1
Faculty of Medicine, Division of
Neurology, University of British
Columbia, Vancouver, British
Columbia, Canada
2
Department of Statistics,
University of British Columbia,
Vancouver, British Columbia,
Canada
3
Multiple Sclerosis Clinic,
University of British Columbia,
Vancouver, British Columbia,
Canada
Correspondence to
Dr E Kingwell, Faculty of
Medicine (Neurology), UBC
Hospital, 2211 Wesbrook mall,
University of British Columbia,
Vancouver, BC V6T 2B5,
Canada; elainejk@mail.ubc.ca
Received 26 May 2011
Revised 13 July 2011
Accepted 16 July 2011
Published Online First
23 August 2011
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Files, which includes registration dates for all BC residents
enrolled in the universal healthcare plan. Patients were followed
until the earliest of death, emigration from BC or study end (31
December 2007). In the event of unsuccessful linkage and
unknown vital status by study end, patients were censored at
their most recent clinic visit.
The University of British Columbia Clinical Research Ethics
Board approved the study.
Statistical analyses
Absolute survival from birth (survival age) and from disease
onset was estimated using the KaplaneMeier method. Survival
was compared between subgroups using the log rank test. For
comparison with observed survival, life expectancy was calcu-
lated for the sex and age matched (at cohort entry) BC general
population from life tables (2000e2002).
20
The potential influence of ascertainment of ‘survivors’during
the early MS clinic years on the estimates and predictors of
absolute survival was assessed by sensitivity analyses.
KaplaneMeier estimates and survival comparisons between
subgroups were repeated after excluding patients with disease
onset prior to 1970. The results of these restricted analyses were
compared with those from the main analyses.
Standardised mortality ratios (SMRs) and corresponding 95%
CIs were used to estimate mortality in the cohort relative to the
general population. Statistics Canada’s mortality rates for BC,
by sex, calendar year and 5 year age band, were used as the
population standard. An SMR greater than 1 indicates an excess
risk of death in the cohort compared with the age, sex and
calendar year matched general population. For all relative
mortality analyses, follow-up began at the first clinic visit.
A Cox regression model for relative mortality
21e23
was used to
examine excess mortality associated with sex, disease course and
onset age. Age, sex and calendar year matched BC general
population mortality rates were entered as time dependent
offsets, and thus excess mortality due to MS was multiplicative
to the general population mortality rates. Results are expressed
as relative mortality ratios (RMRs). An RMR greater than 1
indicates that the mortality ratio for this factor is higher than
that associated with the referent. Potential interactions between
covariates were assessed using stratified analysis.
The relative survival model was also used to explore the
effects of time period of first clinic visit (1980e1985, 1986e1991
and 1992e1997) on survival time within 10 years while taking
into account changing mortality rates in the general population.
Only those patients with cohort entry between 1980 and 1997
were included to allow for comparable 10 year follow-up for
each time period subgroup. To account for varying lengths of
disease duration, relative survival analyses were adjusted for age
at first visit (at cohort entry) in addition to onset age.
21
Statistical analyses were performed using Stata V.11 (Stata-
Corp 2009), R: A Language and Environment for Statistical
Computing V.2.11.1 (R Foundation for Statistical Computing,
Vienna, Austria; 2010) and Statistical Package for the Social
Sciences V.15 (SPSS Inc 2006).
RESULTS
The cohort
Between 1980 and 2004, 6917 patients with definite or probable
MS visited a BC MS clinic. The demographic and clinical char-
acteristics of the cohort are shown in table 1. The ratio of
women to men was 2.6:1; this ratio was 1.3:1 in the PPMS group
and 2.9:1 in the R-MS group. While the median age at disease
onset was 31 years (range 3e75) overall, median onset age was
approximately 12 years greater for PPMS (42 years; range 5e75)
than for R-MS (30 years; range 3e75). Median age at the first
clinic visit was 41 years (range 11e80) and the majority of
patients (65%) were registered within 10 years of MS onset;
16.8% were registered within 1 year.
Most of the patients were never exposed to immunomodu-
latory or immunosuppressive therapy, and 89% of the follow-up
time from disease onset predated exposure. At study end, 1025
(14.8%) patients had died and 5223 (75.5%) were alive. The
remaining 669 patients were censored before study end due to
emigration from BC (7.2%) or no linkage and unknown vital
status (2.5%).
Absolute survival
Overall median survival from onset was 47.5 years (95% CI
45.3e49.7) and median survival age was 76.7 years (95% CI
75.7e77.8). Women (figure 1A), R-MS patients (figure 2A) and
those with a younger onset age (figure 3A) had significantly
longer survival from disease onset. When survival was measured
from birth, women survived to an older age than men (figure
1B). There was, however, no difference in survival age by clinical
course at onset (figure 2B), and older onset patients ($40 years)
survived to an older age than younger onset patients (figure 3B).
When the above analyses were restricted to patients with
onset in 1970 or later (n¼6223), median survival age was
77.4 years (95% CI 76.1 to 78.8). Median survival time from MS
onset was not reached, however 75% survived to 30.3 years from
onset; 2 years less than the equivalent survival time (32.3 years)
for the entire MS cohort. Subgroup comparisons within this
restricted cohort provided similar results to the main analysis.
Table 1 Characteristics of the British Columbia multiple sclerosis
cohort
Patient characteristics (n[6917*) n (%)
Sex
Male 1919 (28)
Female 4998 (72)
Disease course
Relapsing onsety6172 (89)
Primary progressive 694 (10)
Age at symptom onset (years)
<20 646 (9)
20e<30 2415 (35)
30e<40 2205 (32)
$40 1634 (24)
Age (years)
<30z1091 (16)
30d<40 2128 (31)
40e<50 2119 (31)
$50 1579 (23)
Disease duration (years)
<5z3088 (45)
5e<9 1212 (18)
9e<15 1123 (16)
$15 1477 (21)
Time period
1980e1985 1178 (17)
1986e1991 1164 (17)
1992e1997 1767 (26)
1998e2004 2808 (41)
*Clinical course unknown for 51 (1%) patients; age at symptom onset (and hence
disease duration) unknown for 17 (<1%) patients.
yRelapsing onset cohort includes those who later became secondary progressive.
zAge and disease duration measured at cohort entry (date of first visit to a British
Columbia multiple sclerosis clinic).
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Life expectancy relative to the BC population
Expected survival in the age matched BC general population was
84.5 years for women and 80.4 years for men; approximately
6 years longer than that observed in women and men with MS.
The observed and expected survival from disease onset (condi-
tional on surviving to age at first clinic visit) is demonstrated
graphically in figure 4.
Mortality risk relative to the BC population
For the SMR analysis, 6841 patients contributed 77 950 years of
follow-up (76 patients from the original cohort were excluded
because they contributed no follow-up time due to censoring at
their first, and only, clinic visit). Of these 6841 patients, 5223
(76.3%) were followed until the end of the study period, 1025
(15%) until death and 593 (8.7%) until emigration from BC or
their last clinic visit. The mortality risk in the cohort was nearly
three times greater than in the general population (SMR 2.88;
95% CI 2.71 to 3.06). There was a significantly higher mortality
risk for both men and women, and for those with either an
R-MS or PPMS course (table 2). When stratified by onset age,
relative mortality was highest in patients with onset before the
age of 20 years (SMR 4.49; 95% CI 3.67 to 5.51). Relative
mortality decreased with increasing onset age but remained
significant in each age category. Mortality risk was between 2e3
times greater than expected when follow-up was restricted to
the 10 years following cohort entry and stratified by time period
of first visit (table 2).
Relative survival modelling (table 2) showed an increased
mortality risk for PPMS compared with R-MS patients (RMR
1.53; 95% CI 1.30 to 1.80). The excess risk of death was reduced
for those with an older onset age compared with those with
onset before age 20 years. The relative mortality risk for women
was slightly higher than that for men overall. However, further
analysis with separate models for disease course indicated that
there was an interaction between sex and disease course. The
excess hazard for women was 55% higher than for men among
those with PPMS (RMR 1.55; 95% CI 1.19 to 2.01) while the
relative mortality risk for women with R-MS was no higher
than that for men with R-MS (RMR 1.06; 95% CI 0.91 to 1.22).
Time period analysis
Of the 4109 patients with cohort entry between 1980 and 1997,
351 (9%) died within 10 years of their first clinic visit. Although
the crude cumulative survival rate at 10 years was less (88.6%)
for the 1980e1985 cohort than for the 1986e1991 (91.8%) and
1992e1997 (91.7%) cohorts, comparison of relative survival risk
in the later cohorts to the earliest time period cohort provided no
evidence of a change over time (table 2).
DISCUSSION
MS in British Columbia, Canada, was associated with a 6 year
reduction in expected lifespan and with nearly three times the
risk of death compared with the age, sex and calendar year
matched general population. However, we also report some of
Figure 1 KaplaneMeier survival
curves showing survival from onset (A)
and survival age (B) of the British
Columbia multiple sclerosis patients by
sex, with median survival times and
95% CIs.
Figure 2 KaplaneMeier survival
curves showing survival from onset (A)
and survival age (B) of the British
Columbia multiple sclerosis patients by
clinical course (primary progressive
(PPMS) vs relapsing (R-MS)) at onset,
with median survival times and 95%
CIs.
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the longest median survival times in MS, with patients
surviving approximately 48 years from symptom onset and
living to an average age of 77 years (79 years for women and
74 years for men).
Our study is one of the largest of survival with MS and the
largest in North America to date. We have contributed new
findings by examining the average lifespan in MS according to
important clinical and demographic factors, unavailable or
unreported in many previous studies, including the following:
sex, disease course (PPMS and R-MS) and age at symptom onset.
Others have observed a survival disadvantage for MS, ranging
from 6 to 12 years; our estimate is comparable to the
6e7 year survival disadvantage reported in an earlier smaller
Canadian study
12
and slightly less than that reported in other
cohorts.
47910
Differences in these estimates may be explained by
variation in both the clinical characteristics of the MS populations
and the survival expectations of the relevant general population,
as well as assumptions and methods used to estimate expected
survival. However, our finding that MS was associated with
nearly three times the rate of mortality in the general population
is similar to that reported in the majority of European
347e9
and
North American
512
studies. While the SMRs cannot be directly
compared because of potential differences in the age and sex
distribution of cohorts, our findings together with those from
other cohorts, indicate that men and women,
3e57e924
as well as
R-MS and PPMS patients,
7
all have approximately three times
the mortality risk of the general population.
Patients with MS onset at an older age did not survive as long
from disease onset as younger patients, a finding that concurs
with others.
256910
We found, however, that patients who were
older at onset survived to an older age than their younger onset
counterparts. Although this has not previously been demon-
strated by survival studies in MS, studies of disease progression
have reported a similar differential influence of predictors
depending on whether the time to reach specific progressive
milestones is evaluated in terms of age (from birth) or disease
onset.
25e29
In addition, whereas MS patients with a later onset
age ($40 years) had twice the mortality risk of the general
population, mortality risk was four times greater for those with
an early onset (<20 years of age). The relative impact of MS on
mortality is higher in younger adults due to fewer competing
risks for death at a younger age and, by definition, older onset
patients cannot die with clinically recognised MS at a young age.
Overall, patients who are older at disease onset may be consid-
ered to have a better outcome than those with a younger onset;
not only have they lived disease free for a greater number of
years, they can also expect to live to an older age, on average.
In terms of absolute survival, women with MS survived
longer than men, irrespective of whether survival was measured
from birth or onset. A longer survival for women from disease
onset has also been reported for other cohorts,
25713
although
not universally.
1 6 10 14
On the other hand, our relative survival
analysis, which accounts for the shorter life expectancy of men
in the general population, showed that overall, women with MS
fared no better than men with this disease. This also concurs
with observations from other cohorts.
25e7111415
Our findings
were not consistent by disease course, however, and an excess
hazard of death was evident for women with PPMS. The reason
why women with a progressive course from onset carry
a heavier relative mortality burden than men with the same
clinical course is unclear, but warrants further study.
When measured from onset, we found longer survival for
R-MS compared with PPMS. This is consistent with findings
from other studies,
1679e11 14
and is perhaps not surprising
Figure 4 KaplaneMeier survival curves showing survival from onset of
the British Columbia (BC) multiple sclerosis (MS) patients and expected
survival of the BC general population (matched by sex and age at cohort
entry, from 2000 to 2002 mortality rates).
Figure 3 KaplaneMeier survival
curves showing survival from onset (A)
and survival age (B) of the British
Columbia multiple sclerosis patients by
age at disease onset, with median
survival times and 95% CIs.
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considering that symptoms of PPMS typically present at a later
age. On the other hand, we found that PPMS and R-MS patients
survived to the same age; a similar observation was made in the
only other study examining this outcome.
9
Nonetheless,
a greater risk of mortality for those with PPMS became evident
once onset age and the general population mortality risk were
taken into account. The reduced survival time for primary
progressive patients coupled with the extended delays that they
experience to diagnosis or referral to a specialist neurologist
30e32
leaves a relatively brief window of time during which any new
potential interventions that may influence quality of life, disease
progression or mortality can be offered.
We found no evidence of improved relative survival over time
(1980e2007). Survival increased for those with MS but this
improvement mirrored that seen in the general population.
Results were similar for a small Norwegian study
7
although
a small increase in relative survival has been observed in
Denmark since the 1950s.
34
Others have reported either no
evidence of changing trends in MS mortality over time
61314
or
improved survival;
1
these studies did not, however, consider
changes in general population mortality rates.
The potential influence of ascertainment bias was assessed by
estimating survival only for patients with a maximum disease
duration of 10 years when the clinics first opened in 1980,
allowing for a reasonable diagnostic delay of up to 10 years
during that period.
31 33e35
The survival age of these patients was
similar to that of the whole cohort but survival from onset was
approximately 2 years shorter. This is not unexpected and
indicates that our absolute survival estimates may be slightly
longer than that experienced by the incident BC cohort while
the overall estimated survival times still appear robust. None-
theless, direct comparisons of survival estimates from MS
cohorts are complicated by different ascertainment methods
such as whether incidence, prevalence or mixed cohorts are
used.
46e11 14 15 36
We have based our findings, like many others,
on the mixed approach.
The strengths of our study include: the substantial population
of MS patients with 27 years of prospective follow-up and all
with a clinical diagnosis confirmed by an MS specialist neurol-
ogist; and the population based nature of the BC MS database,
which captures approximately 80% of MS patients in BC. The
reasons why the remaining patients do not attend BC MS clinics
are unknown but might include issues with physical access to
the clinics or very mild disease. We have no reason to believe that
the survival of patients who attend BC MS clinics is different to
those who do not. Furthermore, the distribution of sex, age at
onset and clinical course in the BC MS cohort is comparable
with that reported in other MS cohorts.
7 11 18
Linkage of the BC
MS data to BC administrative data ensured reliable coding of
death and minimal loss to follow-up; vital status was unknown
for less than 10% of the patients at the study end due to either
emigration or unsuccessful linkage with the administrative
databases. Some cases with a severe disease course may have
been missed if they died soon after diagnosis but before they
attended a BC MS clinic; this scenario is considered rare and the
potential impact of such severe missed cases is likely to be minor.
The vast majority of patients in the BC MS database are of
Northern European descent; it is estimated that less than 5% of
the cohort is of Asian, North American, Aboriginal or other
ethnicity.
37 38
These findings are therefore mostly generalisable
to MS patients of Northern European descent; other ethnicities
may experience different survival outcomes.
As with any study that relies on diagnosis, identification or
registration of patients some time after symptom onset, our
findings are only generalisable to patients who survive long
enough to be diagnosed with MS and registered at a clinic. Our
study was not designed to address the impact of disease
modifying therapies on mortality, and the cohort included
treated and untreated patients. Very little of the follow-up time
from disease onset post dated first exposure to therapy, however,
and the vast majority of deaths were among unexposed patients;
any potential effects of treatment on the overall findings are
therefore likely negligible.
In summary, we report some of the longest survival times in
MS although the mortality risk was still greater, and the average
lifespan was 6 years shorter, than that seen in the general
Table 2 Standardised mortality ratios and relative mortality ratios for the British Columbia multiple sclerosis cohort
Observed deaths Expected deaths* SMRy(95% CI) RMRz(95% CI) p Value for RMR
Overall (n¼6841x) 1025 356 2.88 (2.71 to 3.06)
Sex
Men 390 146 2.68 (2.43 to 2.96) Referent 1.15 (1.01 to 1.31) 0.03
Women 635 211 3.01 (2.79 to 3.25)
Disease course{
Relapsing onset 784 273 2.87 (2.68 to 3.08) Referent 1.53 (1.30 to 1.80) <0.0001
Primary progressive 236 82 2.89 (2.54 to 3.28)
Age at onset (years)
<20 93 21 4.49 (3.67 to 5.51) Referent
20e<30 288 78 3.71 (3.31 to 4.17) 0.83 (0.65 to 1.04) 0.11
30e<40 304 96 3.16 (2.82 to 3.53) 0.76 (0.60 to 0.96) 0.02
$40 336 162 2.08 (1.87 to 2.31) 0.62 (0.48 to 0.80) 0.0002
Time period (n¼4109)**
1980e1985 126 48 2.60 (2.19 to 3.10) Referent
1986e1991 88 41 2.16 (1.75 to 2.66) 0.81 (0.62 to 1.07) 0.15
1992e1997 137 57 2.42 (2.05 to 2.86) 0.97 (0.76 to 1.24) 0.81
*Sum of the expected deaths within the sex, disease course and age at onset strata may not equal the overall expected deaths (356) due to rounding.
ySMR, standardised mortality ratio. Cohort entry defined as the date of first visit to a British Columbia multiple sclerosis clinic.
zRMR, relative mortality ratio. The multivariable relative survival models included sex, clinical course and age at onset and were adjusted for age at cohort entry.
x76 patients from the original cohort were excluded from these analyses because they were not successfully linked to Ministry of Health Registry and Premium Billing (RP&B) Files, which
includes data and they only visited a British Columbia multiple sclerosis clinic once. Hence they were censored at their first clinic visit and contributed no follow-up time after cohort entry.
{Relapsing onset cohort includes those who later became secondary progressive.
**Standardised mortality ratios and relative mortality ratios for time period represent mortality risk within 10 years of follow-up.
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population. Onset over the age of 40 was associated with
a longer lifespan compared with younger onset patients. While
women lived longer than men with MS, the sex difference
among R-MS patients was no greater than that observed in the
general population. Among those with PPMS, women had
a greater relative survival disadvantage than men; this deserves
further study. Survival within 10 years of first clinic visit
remained stable over 18 years of patient enrolment.
Acknowledgements We are grateful to Tom Duggan, Research Assistant, Division
of Neurology, University of British Columbia, for his help with data manipulation and
coding, and to Population Data BC and the BC Ministry of Health for support with
accessing BC administrative health and Vital Statistics data. Special thanks to the
BC multiple sclerosis clinic neurologists: D Adams, D Craig, L Daly, V Devonshire, S
Hashimoto, O Hrebicek, J Hooge, B Jones, L Kastrukoff, S Meckling, D Parton, D
Paty, A Sayao, P Smyth, W Shtybel, T Traboulsee and to the BC multiple sclerosis
clinic patients for sharing clinical information.
Funding This study was funded by the Canadian Institutes of Health Research
(MOP-82738; PI: HT). EK is funded by a Postdoctoral Fellowship from the Multiple
Sclerosis Society of Canada. AS is funded through grants from the Canadian Institute
of Health Research (MOP-93646; PI: HT) and the National Multiple Sclerosis Society
(RG 4202-A-2; PI: HT), and a Postdoctoral Fellowship from the Multiple Sclerosis
Society of Canada. YZ receives research funding from the Canadian Institutes of
Health Research, the Multiple Sclerosis Society of Canada and the National Multiple
Sclerosis Society. JO receives financial support from the Christopher Foundation
(Vancouver) and the University of British Columbia. HT is funded by the Multiple
Sclerosis Society of Canada (Don Paty Career Development Award); is a Michael
Smith Foundation for Health Research Scholar and the Canada Research Chair for
Neuroepidemiology and Multiple Sclerosis. HT receives research support from CIHR,
the MS Society of Canada and the US National MS Society. The BC MS database has
been funded by an unrestricted grant from Dr Donald Paty and the MS/MRI Research
Group. The funding agencies had no role or involvement in the study design or
conduct, data collection, analysis or interpretation, manuscript preparation or the
decision to submit the paper for publication.
Competing interests EK has received reimbursement of travel and accommodation
costs to present at and attend conferences from the endMS Research and Training
Network, the International Society for Pharmacoepidemiology and Bayer Schering
Pharma. AS has received travel grants to present and attend conferences from the
endMS Research and Training Network and the European Committee for Treatment
and Research in Multiple Sclerosis. JO has received speaker honoraria, consulting
fees, travel grants, research grants or educational grants from Aspreva, Aventis,
Bayer, Biogen-Idec, BioMS, Corixa, Genentech, Novartis, Serono, Talecris and
Teva-neurosciences and receives fees for services from Bayer, Novartis and Biogen
Idec to serve on advisory committees. HT has received research support from the MS
Society of Canada, the US National MS Society, Canadian Institutes of Health
Research and UK MS Trust. She has received speaker honoraria and/or travel
expenses to attend conferences from Consortium of MS Centres, US National MS
Society, Swiss Multiple Sclerosis Society, the University of British Columbia MS
Research Program, Bayer Pharmaceuticals (speaker; honoraria declined) and Teva
Pharmaceuticals (speaker). Unless otherwise stated, HT’s speaker honoraria are
donated to an MS charity or to an unrestricted grant for use by her research group.
Ethics approval This study was conducted with the approval of the University of
British Columbia Clinical Research Ethics Board.
Contributors EK was responsible for designing the study, ensuring the data integrity,
managing the data, statistical analysis, interpretation of the data and drafting the
manuscript. MvdK contributed substantially to the statistical analyses and
interpretation of the data, and drafting and editing of the manuscript. AS provided
intellectual comments and editing of the manuscript. YZ contributed to the statistical
analysis plan and provided intellectual comments and editing of the manuscript. FZ
contributed to the statistical analyses, and to editing of the manuscript. JO provided
intellectual comments and editing of the manuscript. HT obtained funding for the
study, contributed substantially to the study deign and revisions of the manuscript,
and served as a general advisory role. All authors read and approved the final version
of the manuscript.
Provenance and peer review Not commissioned; externally peer reviewed.
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66 J Neurol Neurosurg Psychiatry 2012;83:61e66. doi:10.1136/jnnp-2011-300616
Multiple sclerosis
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online August 23, 2011 2012 83: 61-66 originally publishedJ Neurol Neurosurg Psychiatry
E Kingwell, M van der Kop, Y Zhao, et al.
Canada
sclerosis: findings from British Columbia,
Relative mortality and survival in multiple
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