the ispor task force defined real-world data as:

The ISPOR task force defined real-world data as:

• Data used for decision-making that are not collected in conventional randomized clinical trials

What Is Meant by "Real-World Data?"

Garrison LP, et al. Value Health. 2007;10(5):326-335.

ISPOR = International Society of Pharmacoeconomics and Outcomes Research

Evidence is shaped, while data simply are raw numbers and, alone, are noninformative

• Actual care that patients receive in clinical practice

• All patients must be treated, including those with comorbidities

Garrison LP, et al. Value Health. 2007;10(5):326-335; Nallamothu BK, et al. Circulation. 2008;118(12):1294-1303.

Limitations of Randomized Clinical Trials

Traditional interventional

Real-world observational

Randomized controlled trial

Pragmaticclinical trial

Prospective observational

study

Retrospective observational

study

• Patients treated according to the protocol

• Extensive inclusion and exclusion criteria

• Endpoints are efficacy and safety over a predetermined time period


• Longer-term efficacy and safety data + economic assessments under typical clinical conditions









study


study



• Endpoints are efficacy and safety over a predetermined period of time

• Compare treatment against the standard of care (eg, interferon or glatiramer acetate)


• Possible to compare multiple interventions

• Longer-term efficacy and safety data + economic assessments under typical clinical conditions









study


study



• Pragmatic clinical trials• Prospective observational studies and patient registries• Administrative claims data• Patient surveys• Electronic health records/medical chart reviews• Government- or third-party-sponsored systematic surveys that

assess public health, resource consumption, practice patterns, and clinical trends

Garrison LP, et al. Value Health. 2007;10(5):326-335.

Sources of Real-World Data

a. IMS Health. Gilenya Unique Patient Exposures. 2014. Data on file.b. Henson LJ, et al. CMSC-ACTRiMS 2014. Abstract DX41.c. http://www.tecfidera.com/pdfs/full-prescribing-information.pdf

Drug Approved USA Approved EU World-Wide Exposure

Fingolimod[a] September 2010 March 2011>147,000 patient-years>100,000 patients predominantly in a post-marketing setting

Teriflunomide[b] September 2012 September 2013 6800 patient-years across more than 12 years of the clinical program

Dimethyl fumarate[c] March 2013 January 2014 4603 patient-years in clinical

development

Clinical and Post-Marketing Experience With Oral Therapies

• Noninterventional registry study for prospective compilation of long-term data on safety and efficacy of fingolimod

• 4000 patients with RRMS from neurological clinics and practices throughout Germany

• Recruitment was completed at the end of 2012• Safety and efficacy data will be collected over 5-

year observation period• Pharmacoeconomic data in 800 patients will be

collected for 2 years• Designed according to the Risk Management Plan

of the EMA

Ziemssen T, et al. ECTRiMS 2012. Abstract P522.

PANGAEA

Baseline End ofTreatment

Observational phase

Enrolment of patients

Fingolimod 0.5 mg, n=4000

PANGAEA: Documentation of Fingolimod Treated Patients in a Registry

EMA = European Medicines Agency; RRMS = relapsing-remitting multiple sclerosis

PANGAEA 24-Month Interim Results: ARR by Previous Therapy

Ziemssen T, et al. AAN 2014. Abstract P3.152.

ARR = annualized relapse rate; IFN = interferon

Previous disease modifying therapy Baseline Month 12

All PANGAEA patients (n = 3565/2229) 1.5 0.42

All IFNs (n = 1758/1085) 1.6 0.42

Glatiramer acetate (n = 831/510) 1.6 0.36

Natalizumab (n = 659/412) 0.9 0.6

None/other (n = 317/222) 1.5 0.26

Days Off Treatment: Adherence With Fingolimod

Ziemssen T, et al. ECTRIMS 2012. Abstract P302.

A comparison between PANGAEA and PEARL shows better compliance on fingolimod than on first-line therapy.

DMT = disease-modifying therapy

3 months 6 months 9 months0

0.2

0.4

0.6

0.8

1

1.2

1.4

Other DMTFingolimod

Num

ber o

f Day

s O

ff Tr

eatm

ent

Dur

ing

Last

14

Day

sDuring the last 14 days, how often did you not

take your medication?

MSBase – Fingolimod vs BRACE Therapies: Study Overview[a]

a. Spelman T, et al. ECTRiMS 2013. Abstract P1096.b. Rosenbaum PR and Rubin DB. Biometrika 1983;70:41–55.

• Objective: Assess comparative effectiveness on time to first relapse and to treatment discontinuation in patients with a history of relapses and switching from a BRACE therapy (IFN-β or glatiramer acetate) to fingolimod or another BRACE therapy

• Propensity scores* were used to create balanced cohorts of patients

BRACE = betaferon, rebif, avonex, copaxone, extavia; EDSS = expanded disability status scale; IFN-β = interferon beta

Patients switching from a BRACE therapy to either fingolimod or another BRACE therapy, with at least one relapse in the prior 12 months

(n=518)

1:1 propensity matching of patient characteristics:sex, age, disease duration, EDSS score,

pre-baseline treatment and relapse activity

Unmatched cohorts

Matched cohorts

*Propensity score matching is a statistical technique used to match patients in observational studies[b]

BRACE cohort(n=243)

Fingolimod cohort(n=275)

BRACE cohort(n=208)

Fingolimod cohort(n=208)

0 2 4 6 8 10 120

0.25

0.5

0.75

1BRACE therapies (n=208) Fingolimod (n=208)

Months Since Baseline

Prop

ortio

n of

Pati

ents

N

OT

Rela

psed

MSBASE – Fingolimod vs BRACE Therapies:Proportion of Patients Not Relapsed After Switching

In patients with a history of relapses on BRACE treatment, fingolimod reduced the relapse rate compared with BRACE therapies. Time to first relapse and corresponding risk reduction over 12 months in

patients with history of relapse on DMT treatment*

*Study cohorts were restricted to patients who switched from a BRACE therapy to either fingolimod or to (another) BRACE therapy and had at least 1 relapse in the prior 12 months or at least 2 in the prior 24 months.

Spelman T, et al. ECTRiMS 2013. Abstract P1096.

45% reduction vs BRACE(P < .01)*

0 2 4 6 8 10 120

0.25

0.5

0.75

1BRACE therapies (n=208) Fingolimod (n=208)


Prop

ortio

n of

Pati

ents

N

OT

Dis

conti

nued

MSBASE – Fingolimod vs BRACE Therapies:Discontinuation Rate After Switching

In patients with a history of relapses on DMT treatment, fingolimod reduced the risk of discontinuing treatment compared to BRACE therapies

*Study cohorts were restricted to patients who switched from a BRACE therapy to either fingolimod or to (another) BRACE therapy and had at least 1 relapse in the prior 12 months or at least 2 in the prior 24 months.

Spelman T, et al. ECTRiMS 2013. Abstract P1096.

78% reduction vs BRACE(P < .01)*

Time to discontinuation and corresponding risk reduction over 12 months in patients with history of relapse on DMT treatment*

MSBASE – Real-World Data Comparing Natalizumab vs BRACE Therapies: Study Overview

3976 694

TOP MSBase

3821 694

Original sample

Satisfying entry criteria

3743 694

569 569

Without missing values in the covariates

Successfully matched

Patients4670

4515

4437

1138

All

Completeness of matching 569/694 = 82%

Spelman T, et al. AAN 2013. Abstract P01.211.

"Stay or Go" analysis of 2 data sets using propensity matching

TOP = Natalizumab Observational Program

Selection criteria:• Patients on any BRACE

therapy who had experienced on-treatment relapse during the prior 12 months and who:

– Continued their BRACE therapy or

– Switched to natalizumab

MSBASE – Real-World Data Comparing Natalizumab vs BRACE Therapies: Proportion of Patients Not Relapsed

Spelman T, et al. AAN 2013. Abstract P01.211.

0 0.25 0.5 0.75 10

0.25

0.5

0.75

1MSBase TOP


Prop

ortio

n of

Pati

ents

N

OT

Rela

psed

HR for BRACE vs natalizumab, 2.73; P <.001

Propensity Matched

the ispor task force defined real-world data as:

Documents

value health

clinical practiceall

clinical practicepossible

realworld data

clinical trends garrison

public health

data5ims health

comorbiditiesgarrison