Cost-effectiveness of early initiation of fingolimod versus delayed initiation after 1 year of intramuscular interferon Beta-1a in patients with multiple sclerosis.

Abstract

Fingolimod is a once-daily orally administered disease-modifying therapy (DMT) indicated for treatment of relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical relapses and delay accumulation of physical disability. In the randomized, double-blind, phase 3 TRANSFORMS trial, 0.5 mg/d oral fingolimod substantially reduced relapse frequency when compared with IM interferon-β1a (IFN-β1a) at 12-months. In a 12-month, double-blind, extension phase of the TRANSFORMS study, patients assigned to receive fingolimod continued to receive the same dosage, whereas patients who originally received IM IFN-β1a were randomized to receive either 0.5 or 1.25 mg/d fingolimod.
To investigate the cost-effectiveness of initiating fingolimod therapy early versus after 1 year of IFN-β1a therapy using TRANSFORMS study extension data.
A Microsoft Excel-based model was used to calculate the cost per relapse avoided for 2 years with continuous treatment with fingolimod compared with first-year treatment with IM IFN-β1a and second-year treatment with fingolimod. One-way sensitivity analyses were conducted on key input variables to assess their effect on cost per relapse avoided.
The 2-year relapse rate in the early fingolimod arm was 0.23, and in the delayed fingolimod arm was 0.53. The cost per relapse avoided was $83,125 in the early fingolimod arm versus $103,624 in the delayed fingolimod arm. Results of the sensitivity analyses showed an effect of drug acquisition cost and number of relapses in patients who received no treatment.
Continuous treatment with fingolimod for 2 years resulted in a lower cost per relapse avoided compared with treatment with IM IFN-β1a for the first year and then switching to fingolimod therapy. Thus, delaying fingolimod therapy does not seem to be cost effective.

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Cost-Effectiveness of Early Initiation of Fingolimod Versus
Delayed Initiation After 1 Year of Intramuscular Interferon
Beta-1a in Patients with Multiple Sclerosis
Neetu Agashivala, MS; and Edward Kim, MD, MBA
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
ABSTRACT
Background: Fingolimod is a once-daily orally ad-
ministered disease-modifying therapy (DMT) indi-
cated for treatment of relapsing forms of multiple scle-
rosis (MS) to reduce the frequency of clinical relapses
and delay accumulation of physical disability. In the
randomized, double-blind, phase 3 TRANSFORMS
trial, 0.5 mg/d oral fingolimod substantially reduced
relapse frequency when compared with IM interferon-
?1a (IFN-?1a) at 12-months. In a 12-month, double-
blind, extension phase of the TRANSFORMS study,
patients assigned to receive fingolimod continued to
receive the same dosage, whereas patients who origi-
nally received IM IFN-?1a were randomized to receive
either 0.5 or 1.25 mg/d fingolimod.
Objective: To investigate the cost-effectiveness of
initiating fingolimod therapy early versus after 1 year
of IFN-?1a therapy using TRANSFORMS study ex-
tension data.
Methods: A Microsoft Excel-based model was used
to calculate the cost per relapse avoided for 2 years
with continuous treatment with fingolimod compared
withfirst-yeartreatmentwithIMIFN-?1aandsecond-
year treatment with fingolimod. One-way sensitivity
analyses were conducted on key input variables to as-
sess their effect on cost per relapse avoided.
Results: The 2-year relapse rate in the early fingoli-
mod arm was 0.23, and in the delayed fingolimod arm
was 0.53. The cost per relapse avoided was $83,125 in
the early fingolimod arm versus $103,624 in the de-
layed fingolimod arm. Results of the sensitivity analy-
ses showed an effect of drug acquisition cost and num-
ber of relapses in patients who received no treatment.
Conclusion: Continuoustreatmentwithfingolimodfor
2 years resulted in a lower cost per relapse avoided com-
paredwithtreatmentwithIMIFN-?1aforthefirstyearand
then switching to fingolimod therapy. Thus, delaying fin-
golimod therapy does not seem to be cost effective. (Clin
Ther. 2012;34:1583–1590) © 2012 Elsevier HS Journals,
Inc.Allrightsreserved.
Key words: cost-effectiveness,
feron, multiple sclerosis, treatment.
fingolimod,inter-
INTRODUCTION
Multiple sclerosis (MS) is the most common disabling
neurologic disease in individuals aged 18 to 60 years.1
In the relapsing–remitting form of the disease, exacer-
bations can last for days, weeks, or months, causing
substantial disability and distress. Patients can experi-
ence fatigue, spasticity, sensory disturbances, pain,
ataxia, tremor, bladder and bowel issues, cognitive ef-
fects, weakness, and depression, among other signs
and symptoms that affect daily functioning and affect
quality of life.2
Multiple sclerosis is also associated with a substan-
tial public health burden. The disease has been re-
ported to reduce lifespan on average by 8 years, with
approximately 65% of patients becoming nonambula-
tory 25 years after disease onset.3Symptomatic treat-
ment of relapses, rehabilitative services, and long-term
treatment with disease-modifying therapies (DMTs)
contribute to the economic burden of the disease. In an
analysis of the Nationwide Inpatient Sample of the
Healthcare Cost and Utilization Project database,
288,454 hospital admissions were identified between
1993 and 2006, for an average of 20,604 admissions
annually.3The associated costs per each inpatient epi-
sode increased from $7965 in 1993 to $20,076 in
2006, and are expected to increase as a consequence of
rising health care costs in general.3
Accepted for publication June 14, 2012.
http://dx.doi.org/10.1016/j.clinthera.2012.06.012
0149-2918/$ - see front matter
© 2012 Elsevier HS Journals, Inc. All rights reserved.
Clinical Therapeutics/Volume 34, Number 7, 2012
July 20121583

Page 2

The principal goal of therapy is to prevent or delay
permanent neurologic disability, and early treatment
with DMTs, which can reduce the frequency of exac-
erbations, may prevent the accumulation of disabil-
ity.4,5Currently, 7 DMTs have been approved for
treatmentofMS:2interferon-?1a(IFN-?1a)agents,6,7
2 IFN-?1b agents,8,9glatiramer acetate,10natali-
zumab,11and fingolimod.12Fingolimod is a sphin-
gosine 1–phosphate receptor antagonist that induces
reversible sequestration of lymphocytes in peripheral
lymphatic tissue to modulate the immune response.12
Fingolimod was approved by the US Food and Drug
Administration in September 2010 on the basis of re-
sults of 2 randomized controlled trials, FREEDOMS
(Fingolimod Research Evaluating Effects of Daily Oral
Therapy in MS) and TRANSFORMS (Trial Assessing
Injectable Interferon Versus FTY720 Oral in Relaps-
ing–Remitting Multiple Sclerosis), which found a 54%
reduction in annualized relapse rate (ARR) versus pla-
cebo over 24 months13and a 52% reduction in ARR
versus IM IFN-?1a over 12 months.14
In a 12-month double-blind extension of the
TRANSFORMS study, patients who had received fin-
golimod during the core stage continued taking the
same assigned dosage, whereas patients who had orig-
inally received weekly IM IFN-?1a were randomized
to receive either 0.5 or 1.25 mg/d oral fingolimod.15
In patients entering the extension phase, during year
1, patients receiving 0.5 mg/d fingolimod continu-
ously had an ARR of 0.12, compared with an ARR
of 0.31 in patients who initially received weekly IM
IFN-?1a therapy, and during year 2, ARRs were
0.11 and 0.22, respectively. The 2-year relapse rates
were 0.23 for the continuous fingolimod arm, and
0.53 for the delayed fingolimod arm, respectively,
representing a 57% reduction in relapse risk associ-
ated with earlier initiation of fingolimod.15
A previous study investigated the cost per relapse
avoided over 2 years with fingolimod using a spread-
sheet-based model, and was based on data from the
phase 3 FREEDOMS placebo-controlled trial.16Fin-
golimod was found to be the most cost-effective
agent, costing $74,843 per relapse avoided, com-
pared with SC IFN-?1b ($94,423-102,530), SC IFN-
?1a ($108,940), glatiramer ($124,512), and IM
IFN-?1a ($197,073).16In a sub-analysis using data
from the phase 3 TRANSFORMS core trial, the cost
per relapse avoided over 1 year was $82,016 with
0.5 mg/d fingolimod, compared with $96,282 with
IM IFN-?1a.16One-way sensitivity analysis indi-
cated that the model inputs with the greatest influ-
ence on cost per relapse avoided were fingolimod
drug acquisition costs and the average number of
relapses in patients who received no treatment.16
The present analysis compared the cost-effectiveness
of early versus delayed initiation of fingolimod using
results from the double-blind extension of the
TRANSFORMS trial over the 2-year duration of the
core and extension phases.
METHODS
Model Perspective and Time Horizon
The perspective of the model was that of a US com-
mercial health plan, and, hence, addressed only direct
medical and pharmacy costs. The time horizon was 24
months, consistent with the time frame of the
TRANSFORMS core and extension phases.
Data Sources
This model used the phase 3 12-month core and
12-month extension phases of the TRANSFORMS
trial to compare cost-effectiveness of continuous fin-
golimod therapy vs IFN-?1a for 1 year followed by
fingolimod therapy. The complete methods of the
TRANSFORMS study program have been previously
described.14,15The TRANSFORMS core study en-
rolled patients aged 18 to 55 years with a diagnosis of
relapsing–remitting MS and who had experienced at
least 1 documented relapse in the 2 years before ran-
domization. Enrollment criteria included an expanded
disability status scale (EDSS) score of 0 (normal) to 5.5
(ambulatory for 100 m, and disability precludes full
daily activities),17and neurologic stability, with no ev-
idence of relapse or corticosteroid therapy within 30
days before randomization. Patients could have re-
ceived previous treatment with IFN-? or glatiramer
acetate.
In the core study, patients were randomized to re-
ceive 1 of 3 treatments: 0.5 mg/d oral fingolimod, 1.25
mg/d oral fingolimod, or 30 ?g/wk IM IFN-?1a. Dur-
ing the extension phase, patients who had received fin-
golimod during the core stage continued to receive the
same assigned dose, whereas patients who had origi-
nally received IFN-?1a were randomized to receive ei-
ther 0.5 or 1.25 mg/d oral fingolimod.
Relapsewasdefinedasnew,worsening,orrecurrent
neurologicsymptomsoccurring?30daysfromtheon-
set of a preceding relapse and lasting for at least 24
Clinical Therapeutics
1584Volume 34 Number 7

Page 3

hours without fever or infection. Relapse was con-
firmed if it was accompanied by an increase of at least
one-half point on the EDSS, ?1 point on 2 different
functional systems of the EDSS, or ?2 points on 1 of
the functional systems (bowel, bladder, or cerebral
functional systems were excluded). Only confirmed re-
lapse episodes were counted for the primary efficacy
analysis.
Patients and Disease Outcomes From
TRANSFORMS Extension
A total of 1027 patients entered the extension phase
ofTRANSFORMSandreceiveddrug:356received0.5
mg/d continuous fingolimod; 330 received 1.25 mg/d
continuous fingolimod; and 341 received IFN-?1a
first, then fingolimod.15A total of 882 patients com-
pleted the 24 months of treatment. The relapse rate at
end point was 0.23 in the early 0.5-mg/d fingolimod
group, and 0.53 in the delayed group, resulting in a
57% reduction in risk of relapse with early treatment
with fingolimod versus delayed fingolimod after IFN-
?1a (Table I). A real-world, observational, retrospec-
tive analysis determined that in patients newly initiat-
ing IM IFN-?1a therapy, the relapse rate over the
previous 2 years was 1.53.18On the basis of this rate of
relapse in the untreated population, the number of re-
lapses avoided with early treatment with fingolimod
was calculated as 1.3 and 1.0 with delayed fingolimod
therapy.
Cost-Effectiveness Analysis
A spreadsheet-based model was used to calculate
the cost per relapse avoided with 2 years of continuous
treatment with fingolimod versus 1 year of treatment
with IM IFN-?1a followed by a second year of treat-
ment with fingolimod. In March 2012, wholesale ac-
quisition costs for fingolimod and IM IFN-?1a were
obtained using AnalySource®(Syracuse, New York), a
web-based pricing software tool.19To obtain the net
drug acquisition cost, prescribing information was
usedtodeterminethenumberofdosesperpackageand
the number of packages used per year. The model did
not include product rebates, discounts, or patient co-
pays or co-insurances, and assumed all patients were
100% adherent to treatment.
Monitoring requirements differed between treat-
ments, and were based on each agent’s product pre-
scribing information. A cross-sectional survey con-
ducted in 121 patients with MS was used to obtain the
frequency of neurologist visits for an established pa-
tient.20On the basis of prescribing information for
fingolimod,12all patients new to fingolimod therapy
were assumed to have undergone a 6-hour in-office
observation for signs and symptoms of bradycardia
after the first dose, and an ECG before receiving the
first dose and at the end of the 6-hour first-dose obser-
vation period. Costs for the ECGs were included in the
model. Because all patients new to fingolimod must
have 1 recent (ie, within 6 months) complete blood cell
count (CBC) and 1 liver function test based on the
prescribing information. Two ophthalmologic visits
were also included in the year 1 fingolimod arm per the
monitoring recommendations of the package insert.
Unit monitoring costs were obtained from the 2010
Physician’s Fee and Coding Guide,21and were
$951.00 for a 6-hour in-office observation (1 fingoli-
mod, 0 IFN-?1a), $158.50 for a neurologist visit (2
each), $158.50 for a ophthalmologic visit (2 fingoli-
mod, 0 IFN-?1a), $83.00 for an ECG visit (2 fingoli-
mod, 0 IFN-?1a), $43.00 for a CBC (1 fingolimod, 2
IFN-?1a), $55.00 for a liver function test (1 fingoli-
mod, 2 IFN-?1a), and $181.50 for a thyroid panel (0
fingolimod, 1 IFN-?1a). The cost of other potential
monitoring requirements for patients at high risk, such
as dermatology visits and pregnancy tests, and tests
commonly required for diagnosis of MS, were not in-
Table I. Relapse inputs.
Model
Parameter
Early
Fingolimod
Arm
Delayed
Arm: Year 1,
IFN-?1a Year 2,
Fingolimod
Relapse rate
Year 1
Year 2
2-Year total
relapse rate
2-Year relapse
rate before
treatment
0.12
0.11
0.31
0.22
0.230.53
1.53
No. of relapses
avoided 1.31.0
IFN ? interferon.
N. Agashivala and E. Kim
July 20121585

Page 4

cluded in the model. Similarly, costs of extended first-
dose monitoring for patients receiving fingolimod who
had some pre-existing conditions were not included
because of lack of clarity on the percentage of such
patient populations. However, the effect of changes in
monitoring costs was included in the sensitivity analy-
ses. Monitoring costs were calculated for the 2-year
time horizon to account for patients who were new to
therapy and receiving existing therapy each year.
The cost of relapse was based on the cost of man-
aging the relapse, as well as the intensity of the re-
lapse. The direct cost of low-, moderate-, and high-
intensity relapse management was obtained using
the method of O’Brien et al.22Low-intensity relapses
were defined as those requiring a physician office
visit, treatment with symptom-related medication,
and a follow-up visit. Medium-intensity relapses
were defined as those requiring a physician office or
emergency department visit, treatment with IV
methylprednisone and symptom-related medica-
tions, and a follow-up office visit or consultations
with a physical, occupational, or speech therapist.
High-intensity relapses were defined as those requir-
ing a physician office or emergency department visit,
treatment requiring hospital admission, and post-
discharge services including outpatient follow-up,
rehabilitation, home health care, skilled nursing fa-
cility care, and short-stay nursing home care, or hos-
pital readmission within 30 days. The relative inci-
dence of each relapse severity was obtained from the
EVIDENCE(EVidence
sponse: European North American Comparative Ef-
ficacy) trial.
One-way sensitivity analyses were conducted on
key input variables to assess their effect on cost per
relapse avoided. Univariate analyses were performed
by varying each model input by 10% around the
base-case value while keeping the other inputs
constant.
forInterferonDose-re-
RESULTS
Cost Savings
On the basis of prices obtained using the method of
O’Brien et al22and the incidence of relapse severity
based on the EVIDENCE trial, the cost of a relapse
adjusted to 2011 US dollars was calculated at
$5090.83. On the basis of risk of relapse with each
treatment derived from the TRANSFORMS extension
phase, 2-year relapse costs were $1170.89 in the early
fingolimod group and $2698.14 in the delayed-treat-
ment group. The cost of relapse in the early fingolimod
group was $610.90 for the first year, and $559.90 for
the second year, and in the delayed fingolimod group
was $1578.20 for the first year, and $1119.90 for the
second year. Treatment costs were $52,362.90 for a
year of fingolimod therapy, and $46,020.00 for a year
of IFN-?1a therapy (Table II).
Monitoring costs differed by year and by treat-
ment. Monitoring costs for treatment with fingoli-
mod was calculated at $1849.00 for the first year,
and at $317.00 for the second year. Monitoring
costs for treatment with IM IFN-?1a were $694.50
for the first year (Table II). Total costs (drug acqui-
sition, monitoring, and relapse-related costs) were
$108,062.69 in the early fingolimod group, and
$103,624.54in thedelayed
(Table I). The cost per relapse avoided was lower in
the early fingolimod group, at $83,125.00, com-
pared with $103,624.00 in the delayed fingolimod
group. The cost per relapse avoided was $20,499.00
more in the delayed fingolimod group than in the
early fingolimod group (Figure 1).
treatmentgroup
Sensitivity Analyses
Model parameters used in the sensitivity analyses
included relapse rates during treatment, number of re-
lapses in untreated patients, cost per relapse, monitor-
Table II. 2-Year costs of early fingolimod vs de-
layed fingolimod therapy.
Model Parameter
Early
Fingolimod Arm
Delayed Arm:
Year 1, IFN-?1a
Year 2, Fingolimod
Treatment cost
Year 1
Year 2
$52,362.90
$52,362.90
$46,020.00
$52,362.90
Monitoring cost
Year 1
Year 2
$1849.00
$317.00
$694.50
$1849.00
Relapse cost while
receiving drug
Total cost*
$1170.89
$108,062.69
$2698.14
$103,624.54
IFN ? interferon.
*Total cost ? treatment cost ? monitoring cost ? re-
lapse cost while receiving drug.
Clinical Therapeutics
1586 Volume 34 Number 7

Page 5

ing, and drug acquisition costs (Figure 2). The model
inputs with the largest effect on the primary cost anal-
ysis were the number of relapses in the untreated pa-
tient population, drug acquisition costs of fingolimod
and IM IFN-?1a, and the cost of a relapse (Figure 2).
Therelapserateinthedelayedfingolimodarmalsohad
an impact, as well (Figure 2).
DISCUSSION
These model results found that continuous treat-
ment with fingolimod for 2 years resulted in a lower
cost per relapse avoided compared with initiating
fingolimod therapy after 1 year of treatment with IM
IFN-?1a. Cost per relapse avoided over the 2-year
horizon of the present study was considered a rele-
vant measure of cost-effectiveness, even though MS
is a chronic condition, because in the United States,
the mean length of continuous health plan enroll-
ment is ?2 years.23While a longer time frame that
incorporates costs associated with disability pro-
gression may be more robust, such a long time frame
may not be relevant from the perspective of a US
commercial health plan. Recently published results
of a modified Delphi panel recommended restricting
patient access to fingolimod therapy and preferen-
tially using interferons and glatiramer acetate as
first-line therapies.24However, fingolimod had been
available for only ?3 months when the panel met,
and a lack of awareness of the safety profile of fin-
golimod compared with well-established self-in-
jected therapies seems to have contributed to this
position.24Results of the current model suggest that
such plan designs may not be cost-effective. Under
such circumstances, the differences in drug acquisi-
tion costs may be offset in part by relapse-related
costs. However, the 52% reduction in ARR of fin-
golimod versus IFN-?1a during year 1 is the primary
reason for the cost-effectiveness of continuous fin-
golimod therapy.
Continuing treatment with a less efficacious medi-
cation is not recommended in the presence of subopti-
mal clinical response,25-28and given the demonstrated
superiority of fingolimod as compared with weekly IM
IFN-?1a with respect to ARR, initiating treatment
with IM IFN-?1a poses several concerns beyond
higher costs per relapse avoided. There is increasing
evidence that relapse prevention is a key component in
delaying the progression of neurologic disability in
MS. A recent meta-analysis of 19 clinical trials encom-
passing 44 arms, 25 contrasts, and 10,009 patients
found a strong correlation between relapses and dis-
ability,witha50%relativereductionintheoccurrence
of relapses, leading to a 30% relative reduction in the
risk of worsening of the EDSS score.29
The present model has a number of limitations.
First, relapse data were derived from a clinical trial,
and may differ from what is observed in clinical
practice, as found in an investigation of costs asso-
ciated with the management of colorectal cancer30;
however, evidence of this in MS is lacking. This
model assumed 100% adherence to DMTs, which is
much higher than rates reported in real-world set-
tings.20Fingolimod is the only oral DMT currently
available for treatment of MS, and may have differ-
ent adherence rates than injectable DMTs. Because
adverse effects of self-injected DMTs have been
identified as a substantial barrier to adherence, the
introduction of an oral medication may lead to
greater adherence31; however, we elected to choose
the conservative approach of assuming equal adher-
ence with all treatments regardless of differences in
the adverse effect profile. Because most adverse
events reported in clinical trials of fingolimod were
generally mild and required minimal or no medical
interventions, the model did not consider the costs of
treating DMT-related adverse events. In addition,
the effect of disability progression was not included
in the model because the model evaluated the costs
of care for a patient with MS over a short (2-year)
period, and costs of disability progression are gener-
ally incurred over a longer period (?10 years). Nev-
$0
Early Fingolimod Arm
$83,125
Difference
$20,499
Delayed Fingolimod Arm
$103,624
$20,000
$40,000
$60,000
$80,000
$100,000
$120,000
Figure 1. Costperrelapseavoided.(Costperrelapse
avoided ? total costs/relapse avoided.)
N. Agashivala and E. Kim
July 2012 1587

Page 6

ertheless, the 2-year time horizon was thought ade-
quate to assess cost-effectiveness because most
adverse events occur early in the course of treatment
and diminish over time, and a shorter time horizon is
consistent with member turnover observed in US
commercial health plans. Using one-way sensitivity
analysis limited insights into the influence of each
variable individually, and did not test the effects of
multiple variables, which would have been more rep-
resentative of a real-world scenario; however, this
analysis used clinical trial data and was meant to
represent a best-case scenario. An early report eval-
uating conflicts of interest in economic analyses of
drugs used in oncology found that there was a re-
duced likelihood of reporting unfavorable results if
the economic analysis was associated with industry
sponsorship.32However, we believe our method is
sound and based on established principles of phar-
macoeconomic analysis. In addition, expansion of
the earlier literature analysis found that operational
aspects of pharmaceutical-sponsored trial reporting
were more robust than that of nonprofit-sponsored
studies, and that the original conclusions may have
been the result of a difference in focus between phar-
maceutical-sponsored studies that focused primarily
on clinical trial data and nonprofit-sponsored stud-
ies that focused on more academic or practice
settings.33
CONCLUSIONS
Results of this trial-based economic model demon-
strate that continuous treatment with fingolimod is
more cost-effective than treatment with weekly IM
IFN-?1a and then switching to fingolimod therapy.
Formularydesignsthatrestrictfingolimodtolaterlines
of therapy may not be economically efficient.
2-Year relapse rate if untreated$74,372
WAC of fingolimod$75,069
2-Year early fingolimod relapse rate$81,680
2-Year monitoring costs$82,959
Cost of a relapse
2-Year relapse rate if untreated
B
A
2-Year delayed fingolimod relapse rate
WAC of fingolimod
WAC of INF-β 1a
Cost of a relapse
2-Year monitoring costs
$89,874 $122,343
$98,409$109,424
$98,388$108,861
$99,023
$108,227
$103,355
$103,894
$103,370
$103,879
$70,000
$85,000$95,000 $105,000$115,000$125,000
$75,000 $80,000$85,000$90,000 $95,000
$83,035$83,215
$83,292
$84,622
+10%
–10%
$91,181
$94,213
+10%
–10%
Figure 2. Sensitivity analyses of cost per relapse avoided with early fingolimod therapy (base case, $83,125)
(A) and delayed fingolimod therapy (base case, $103,624) (B). WAC ? wholesale acquisition
costs.
Clinical Therapeutics
1588 Volume 34 Number 7

Page 7

ACKNOWLEDGEMENT
We thank Meredith Rogers, MS, and Michelle Adams,
BSJ, MAIA who provided writing and editorial assis-
tance. Ms. Agashivala and Dr. Kim initiated the study,
participated in the definition of study objective and
search strategy, conducted the analysis and interpreta-
tion of results, and wrote and critically reviewed the
manuscript. This research was funded internally by
Novartis Pharmaceuticals Corporation. All authors
have agreed to conditions noted on the Authorship
Responsibility form, are in congruence with Ethical
Adherence, and have read and approved the entire
manuscript.
CONFLICTS OF INTEREST
Ms.AgashivalaandDr.KimareemployeesofNovartis
Pharmaceuticals Corporation. Funding for develop-
ment of the manuscript was provided by Novartis
Pharmaceuticals Corporation to Write All, Inc, to help
in editorial and written preparation of the manuscript.
Ms. Adams is an employee of Write All, Inc, and Ms.
Rogers is a contracted writer for Write All, Inc.
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Address correspondence to: Neetu Agashivala, MS, Novartis Pharmaceuticals
Corp, Health Economics & Outcomes Research, 405-4024A, One Health
Plaza,EastHanover,NJ 07936-1080.
novartis.com
E-mail: neetu.agashivala@
Clinical Therapeutics
1590 Volume 34 Number 7