Implementation of a Multinational Study of Adherence to Treatment in Multiple Sclerosis Patients: Fr

1
Implementation of a Multinational Study of
Adherence to Treatment in Multiple Sclerosis
PatientsFrom Challenge to Success

• Global Adherence Project GAP
• A multicenter observational study on adherence to
  Disease Modifying Therapies in patients suffering
  from Relapsing Remitting Multiple Sclerosis

May 2007
2
TNS Healthcare At a Glance.

• One of the worlds largest full-service research
  and consulting firms
• Significant healthcare focus since inception over
  three decades ago
• Over 8,000 studies in pharmaceuticals,
  diagnostics, biotech and managed care for over
  150 clients
• Proprietary panels enabling broad access to
  physicians and patients in Europe and North
  America
• TNS Healthcare is a well-recognized name in
  clinical/outcomes research in Europe
• Presence in 70 countries worldwide with over
  14,000 employees
• Widest global reach with the deepest local
  knowledge of regulatory issues and healthcare
  systems

3
Global Adherence Project GAP Background

• Benefits of medicine may be compromised by poor
  adherence
• Only about 50 of patients with chronic diseases
  in developed countries adhere to recommended
  treatment1
• Disease Modifying Therapies (DMTs) constitute the
  backbone of Multiple Sclerosis (MS) treatment.2
• Persistence and adherence rates to MS therapy are
  higher in clinical trials than in the real world
  3
• Limited data is currently available on the real
  world adherenceto MS therapies among
  geographically culturally diverse populations
• The key patient-related, therapy-related and
  health care provider-relatedfactors that
  contribute to low adherence in the real world are
  unknown

4
Global Adherence Project GAPObjectives
Primary To evaluate patient adherence rates to
the approved DMTs for relapsing-remitting MS
(RRMS) among geographically culturally diverse
patient populations

• Secondary
• To explore the following factors that influence
  adherence to DMTs in the study population
• Social and economic factors
• Health system / healthcare team factors
• Disease / therapy related factors
• Patient related factors
• Quality of life, cognition and depression

Results from preliminary analyses will be shared
in this presentation
5
Global Adherence Project GAPStudy Design

• Observational
• Cross sectional
• Controlled
• Multinational22 countries in Europe, Latin
  America, Canada, Asia and Australia

6
Global Adherence Project GAPParticipating
Countries

• North America
• Canada
• Central and South America
• Argentina, Brazil,Mexico, Venezuela
• Middle East
• Iran, Israel
• Oceania
• Australia

• Southern Europe
• Portugal, Spain, Italy
• Northern Europe
• Belgium, Denmark, Ireland,Netherlands, Sweden,
  UK
• Central and Eastern Europe
• Austria, Czech Republic,Germany,
  France,Switzerland

7
Global Adherence Project GAPStudy Inclusion
and Exclusion Criteria

• Key inclusion criteria
• Patients 18 years of age with
• Documented diagnosis of RRMS
• Monotherapy with current DMT for gt 6 months

• Key exclusion criteria
• Progressive MS
• Inability to complete any study component
• Involvement in clinical or investigational drug
  studies within 6 months
• Treatment with immunosuppressive regimens or IVIG
  within the last 12 months

8
Global Adherence Project GAPOutcome Measures
Physician Survey

• Site-specific, practice-related survey
• Infrastructure
• Role of nurse
• Treatment paradigms
• Education on disease and treatment
• Adherence factors

9
Global Adherence Project GAPOutcome Measures
Physician Survey

• Patient-related survey
• Disease history and current status
• Treatment history
• Degree of impairment
• Current therapy

10
Global Adherence Project GAPOutcome Measures
Patient Survey

• Details on current disease status, treatment
• and factors affecting adherence evaluated
• Demographics
• Education
• Social support structure
• Education on MS and DMTs
• Views on medical management
• Reasons for non-adherence
• Complications

11
Global Adherence Project GAPOutcome Measures
MS International Quality of Life (MusiQoL)
Questionnaire4

• Measurement of
• Presence and severity of MS symptoms
• Patient perception of disease and treatment
• Assessments include
• Physical well being
• Psychological well being
• MS symptoms
• Self-esteem
• Relationships with friends
• Relationships with family and medical staff

12
Global Adherence Project GAPOutcome Measures
Neuropsychological Screening Questionnaire
(MSNQ)5

• Sensitive and specific predictor of
  neuropsychological impairment
• Cognition
• Depression
• Questions involve
• Ability to focus
• Forgetfulness
• Comprehension
• Emotions
• Validated in English only

13
Global Adherence Project GAPChallenges Study
Design
Observational non-interventional
study? Interventional Study? Phase
IV? Epidemiological study?
Consequencesof country specificrequirements
14
Global Adherence Project GAPChallenges Study
Design

• Legal One persons trash is another persons
  treasure
• No requirements at all
• Expectations exactly like in a clinical Trial

• Ethics A trip through a multicultural
  landscape
• No need for ethical approval
• 1 local approval for all the sites
• 1 central approval
• Local approvals
• Central and local approvals

15
Global Adherence Project GAPChallenges
Information to be collected in a multicultural
scenario

• Questionnaire Content
• Specific National Health Systems ? Social and
  economic factors
• Educational System ? Patient related factors
• Market situation ? Therapy related factors

• Translation
• Central translation forward / backward
• Local validation specific medical terminology /
  patient terminology

16
Global Adherence Project GAPChallengesInforma
tion to be collected in a multicultural scenario

• Paper based / Internet?
• Country differences
• Patient selection / bias

• Validation
• MusiQol
• MSNQ

17
Global Adherence Project GAPChallenges
Pre-enrollment activities

• Recruitment
• Hospitals
• Office based
• Health system neurology competency centers

• Contracts
• Hospital standards
• Office based

18
Global Adherence Project GAPChallenges
Pre-enrollment activities

• Training
• Investigator status
• Face to face vs CD training
• Qualification of training staff
• Personal expectations

• Logistics
• Country specific aspects

19
Global Adherence Project GAPChallenges How to
guarantee and maintain standards for consistent
communication and tracking

• Sponsor
• Reporting and tracking of pre enrollment
  activities and project progress and milestones
• TNS Healthcare
• Coverage of whole project cycle integrating
  project and data management into a single
  platform with definite interface to local
  affiliates
• Sites
• Site management by locals, newsletter, and query
  processing

20
Global Adherence Project GAPTNS Tasks

• Study implementation in all countries
• Training of local TNS affiliates face to face
  meetings,briefings, conference calls, training
  CD
• Notification to local authorities
• Submissions to IRB/EC and follow up
• Study implementation in the sites
• Local formalities, investigator contract, training

21
Global Adherence Project GAPTNS Tasks (cont.)

• Delivery of study documents to the sites
• GAP database (InDrums) set up, including Status
  Reports
• Weekly enrollment status to the sites and sponsor
  affiliates via email
• Monthly newsletters to the sites and sponsor
  affiliates via mail
• Local support to the sites

22
Global Adherence Project GAPTNS Tasks (cont.)

• Safety monitoring (local and central)
• Generation of queries and forwarding to the
  investigators for resolution (local)
• Investigators remuneration (local)
• Data management (central)
• Statistical analysis

23
Global Adherence Project GAPStudy Process Flow
24
Global Adherence Project GAPResults
25
Global Adherence Project GAPBaseline Patient
Characteristics
26
Global Adherence Project GAPAdherence Rate
Range66 - 85
Adherent patients
Note Adherence was defined as not missing 1 DMT
injection or changing dose within 4 weeks prior
to survey
27
Global Adherence Project GAPReasons for
Non-adherence
of patients
32 of patients reported at least one
injection-related reason for missing or changing
their DMT dose
Patients could have reported more than 1 reason
for non-adherence. When counting
injection-related reasons for non-adherence, each
patient was counted only once.
28
Global Adherence Project GAPAdherence Rate by
Disease Treatment Duration
29
Global Adherence Project GAPMSNQ Adherent
vs. Non-adherent patients
P 0.0002
Median Total Score
Adherent n 301
Non-adherent n 175
30
Global Adherence Project GAPMusiQoL - Adherent
vs Non-adherent Patients
Worst
Best
31
Global Adherence Project GAPStudy Conclusions
(preliminary results)

• Study findings confirmed that treatment adherence
  is an issue in MS and that there are factors
  related to therapy that should be considered when
  choosing a therapy to facilitate adherence
• 75 of the treated patients showed adherence to
  the therapy
• Forgetting to administer injection was the most
  commonly cited reason for non-adherence (50 for
  non adherent, 12.6 for all patients), which may
  be related to the complexity of treatment
  regimens or lower cognitive function in non
  adherent patients
• Injection-related reasons were the next most
  frequently cited reason for non-adherence, with
  32 of patients reporting at least 1
  injection-related issue (8 of all patients).

32
Global Adherence Project GAPConclusions
(preliminary analysis)

• Compared with non-adherent patients, adherent
  patients had shorter disease duration, shorter
  treatment, and fewer problems associated with
  injection-site reactions.
• Adherence patients had a better quality of life
  than non-adherent patients.
• Adherent patients had fewer neuropsychological
  problems than non adherent patients.

33
Global Adherence Project GAPA TNS Healthcare
Success Story

• Prior to planning an international project,
  check the local /national particulars to avoid
  unexpected inconveniences
• Clarify goals and the means to reach them
• Integrate all stakeholders and understand their
  expectations
• Set up team and rules and implement team spirit
• Create a sense of ownership
• Set up milestones and celebrate successes
• Be flexible

34
Global Adherence Project GAPA TNS Healthcare
Success Story

• Do not forget that working across multiple
  countries demands
• Local presence in the countries with deep
  knowledge of the legal and regulatory environment
  and local language help-desk support throughout
  the project
• Centralized project management including data
  management and quality control to ensure standard
  operating procedures through the whole landscape
• Proven web-based technical support for
  monitoring, tracking and management of all
  project activities and for communication through
  all the parties involved in the project
• And last but not least dont give up and dont
  panic

35
Global Adherence Project GAPReferences

• Burkhart PV, Sabate E. Adherence to long-term
  therapies evidence for action. J Nurs Scholarsh.
  2003 35(3)207.
• Jacobs LD, Cookfair DL, Rudick RA et al.
  Intramuscular interferon beta-1a for disease
  progression in relapsing multiple sclerosis. The
  Multiple Sclerosis Collaborative Research Group
  (MSCRG)Ann Neurol. 1996 Mar 39(3)285-94.
• From compliance to adherence in long-term MS
  therapies. EMSP Seminar, Brussels, October 2004.
• P. Auquier, A. Beresniak, O. Fernandez, et al.
  Validation of the Multiple Sclerosis
  International Quality of Life (MusiQoL)
  questionnaire. ECTRIMS Sept 28 Oct 01, 2005.
  Poster presentation.
• Benedict RH, Cox D, Thompson LL et al. Reliable
  screening for neuropsychological impairment in
  multiple sclerosis. Mult Scler. 2004
  Dec10(6)675-8.

36
Thank you for your attention!