1. What Is Meant by "Real-World Data?"
The ISPOR task force defined real-world data as:
Data used for decision-making that are not collected in conventional randomized clinical trials
Evidence is shaped, while data simply are raw numbers and, alone, are noninformative
ISPOR = International Society of Pharmacoeconomics and Outcomes Research
Garrison LP, et al. Value Health. 2007;10(5):

2. Limitations of Randomized Clinical Trials
Traditional interventional
Real-world observational
Randomized controlled trial
Pragmatic clinical trial
Prospective observational study
Retrospective observational study
Patients treated according to the protocol
Actual care that patients receive in clinical practice
Extensive inclusion and exclusion criteria
All patients must be treated, including those with comorbidities
Garrison LP, et al. Value Health. 2007;10(5): ; Nallamothu BK, et al. Circulation. 2008;118(12):

3. Limitations of Randomized Clinical Trials
Traditional interventional
Real-world observational
Randomized controlled trial
Pragmatic clinical trial
Prospective observational study
Retrospective observational study
Patients treated according to the protocol
Actual care that patients receive in clinical practice
Extensive inclusion and exclusion criteria
All patients must be treated, including those with comorbidities
Endpoints are efficacy and safety over a predetermined time period
Longer-term efficacy and safety data + economic assessments under typical clinical conditions
Garrison LP, et al. Value Health. 2007;10(5): ; Nallamothu BK, et al. Circulation. 2008;118(12):

4. Limitations of Randomized Clinical Trials
Traditional interventional
Real-world observational
Randomized controlled trial
Pragmatic clinical trial
Prospective observational study
Retrospective observational study
Patients treated according to the protocol
Actual care that patients receive in clinical practice
Extensive inclusion and exclusion criteria
All patients must be treated, including those with comorbidities
Endpoints are efficacy and safety over a predetermined period of time
Longer-term efficacy and safety data + economic assessments under typical clinical conditions
Compare treatment against the standard of care (eg, interferon or glatiramer acetate)
Possible to compare multiple interventions
Garrison LP, et al. Value Health. 2007;10(5): ; Nallamothu BK, et al. Circulation. 2008;118(12):

5. Sources of Real-World Data
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):

6. Clinical and Post-Marketing Experience With Oral Therapies
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
IMS Health. Gilenya Unique Patient Exposures Data on file.
Henson LJ, et al. CMSC-ACTRiMS Abstract DX41.

7. PANGAEA: Documentation of Fingolimod Treated Patients in a Registry
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
PANGAEA
Observational phase
End of Treatment
Baseline
Fingolimod 0.5 mg, n=4000
Enrolment of patients
EMA = European Medicines Agency; RRMS = relapsing-remitting multiple sclerosis
Ziemssen T, et al. ECTRiMS Abstract P522.

8. PANGAEA 24-Month Interim Results: ARR by Previous Therapy
Previous disease modifying therapy
Baseline
Month 12
All PANGAEA patients (n = 3565/2229)
1.5
0.42
All IFNs (n = 1758/1085)
1.6
Glatiramer acetate (n = 831/510)
0.36
Natalizumab (n = 659/412)
0.9
0.6
None/other (n = 317/222)
0.26
ARR = annualized relapse rate; IFN = interferon
Ziemssen T, et al. AAN Abstract P3.152.

9. Days Off Treatment: Adherence With Fingolimod
During the last 14 days, how often did you not take your medication?
Number of Days Off Treatment During Last 14 Days
A comparison between PANGAEA and PEARL shows better compliance on fingolimod than on first-line therapy.
DMT = disease-modifying therapy
Ziemssen T, et al. ECTRIMS Abstract P302.

10. MSBase – Fingolimod vs BRACE Therapies: Study Overview[a]
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
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)
Unmatched cohorts
BRACE cohort (n=243)
Fingolimod cohort (n=275)
1:1 propensity matching of patient characteristics:
sex, age, disease duration, EDSS score,
pre-baseline treatment and relapse activity
Matched cohorts
BRACE cohort (n=208)
Fingolimod cohort (n=208)
*Propensity score matching is a statistical technique used to match patients in observational studies[b]
BRACE = betaferon, rebif, avonex, copaxone, extavia; EDSS = expanded disability status scale;
IFN-β = interferon beta
a. Spelman T, et al. ECTRiMS Abstract P1096.
b. Rosenbaum PR and Rubin DB. Biometrika 1983;70:41–55.

11. 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*
45% reduction vs BRACE
(P < .01)*
*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 Abstract P1096.

12. 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
Time to discontinuation and corresponding risk reduction over 12 months in patients with history of relapse on DMT treatment*
78% reduction vs BRACE
(P < .01)*
*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 Abstract P1096.

13. MSBASE – Real-World Data Comparing Natalizumab vs BRACE Therapies: Study Overview
"Stay or Go" analysis of 2 data sets using propensity matching
All
Patients
TOP
MSBase
Original sample
3976
694
4670
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
3821
694
4515
Satisfying entry criteria
Without missing values in the covariates
3743
694
4437
569
569
1138
Successfully matched
Completeness of matching 569/694 = 82%
TOP = Natalizumab Observational Program
Spelman T, et al. AAN Abstract P

14. HR for BRACE vs natalizumab,
MSBASE – Real-World Data Comparing Natalizumab vs BRACE Therapies: Proportion of Patients Not Relapsed
Propensity Matched
HR for BRACE vs natalizumab,
2.73; P <.001
Spelman T, et al. AAN Abstract P