Transcript PowerPoint - KoNECT International Conference 2016

Rare Disease Clinical
Research: Collaboration
The Key To Success
Cinzia Dorigo
Executive Director Rare Disease
Italy
INC Research
Rare Disease Clinical
Development Landscape
The challenges of Rare Disease
• Typically chronic, progressive, degenerative, often disabling and
sometimes life-threatening.
• Patient should not be denied treatment just because of rarity
• Time to diagnosis and access to potential treatment option
• The pharmaceutical industry needs special incentives to research,
develop and commercialize products
Orphan Drug Enabling Legislation,
Designation Criteria, and Industry Incentives
Legislation and Provisions US (FDA)
EU (EMA)
Orphan Drug Legislation or Orphan Drug Act
Policy
1983
Regulation on Orphan
Orphan Drug Program Orphan Drug Regulation
Medicinal Products 1999 1997
1993
Marketing Exclusivity
Period
10 years (extended by 2 y 5 years
ears for medicines that al
so comply with required
pediatric investigations)
10 years
Accelerated Evaluation
Yes
Availability
Application or Other
Yes
Regulatory Fee Reductions
or Waivers
Yes
Yes
Yes
Yes
Yes
No
Scientific Advice (Research Yes
Protocols, Technical
Assistance, etc.)
Yes
Yes
Yes
Tax Incentives
Tax credits developed by No
each member state
Other
7 years
50% tax credits for
clinical research
costs
Clinical research
funding through
Orphan Products
Grants Program
Voucher program
Australia (TGA)
Japan (MHLW)
Tax Exemption Law (12%
of expenses)
Access to EU centralized Non-financial incentives Extension of registration
authorization process
include pre-licensing
validity period
Additional incentives for access and Regulatory Development costs
micro, small, and
Assistance
partially reimbursed
medium-sized enterprises
, including administrative
and procedural assistance
, and fee reductions
USA, EU and Japan OD Designation
USA, EU & Japan Designations per Year (1983-2014)
Source: EvaluatePharma® 30 September 2015
300
Designation Per Year
250
200
150
Strong Increase from 2003
100
USA, EU & Japan Designations Cumulative Total
Source: EvaluatePharma® 30 September 2015
3,500
2,500
2,000
1,500
1,000
500
Japan Designations Total
2014
2013
2012
2011
2010
2009
2008
2007
2006
2005
2004
2003
2001
EU Designations Total
2002
2000
1999
1998
1997
1996
1995
1994
1993
1992
1991
1990
1989
1988
1987
1986
1985
1984
0
1983
Total Designations
3,000
USA Designations Total
2014
2013
2012
2011
2010
2009
2008
2007
2006
2005
2004
2003
2001
2002
1999
2000
1998
1997
1996
1994
1995
1993
1992
1991
1990
1988
1989
1987
1986
1985
1984
0
1983
50
OD Designation by Therapeutic Area
Analysis of R&D opportunities from 50
Large Pharma (pipeline data
updated at 2015)
Worldwide Orphan Drug Sales 2000-2020
Worldwide Orphan Drug Sales & Share of Prescription
Drug Market (2000-2020)
200
25%
20.2%
180
WW Prescription Sales ($bn)
160
20%
140
120
15%
+11.7% CAGR 2015-20
100
80
60
10%
6.1%
40
5%
20
0
0%
2000
2001
2002 2003 2004 2005 2006 200
7
2008 2009
WW Orphan Sales
2010
2011
2012
2013
2014
WW Orphan as % of WW Rx
2015
2016
2017
2018
2019
2020
WW Orphan Sales as a % of WW Rx Sales (excl. Generics)
Source: EvaluatePharma® 30 September 2015
Collaboration The Key To
Success
Collaborative approach to address the
challenges of rare diseases clinical research
Rare Diseases Clinical Research
High complexity - Multiple stakeholders
Physicians
Sponsor
Patients
Prescribers
Providers
Researchers
Payers
Academic R
esearchers
Caregivers
Advocacy
groups
Regulators
Sponsors
Site Investi
-gators
Focusing basic, clinical, operational, and regulatory science towards the acceleration of clinic
al research and availability of meaningful therapies for patients with Rare Diseases
© 2016 INC Research Holdings, Inc.
10
Critical dependence in Rare Disease
Research
Valid scientific
hypothesis and
ability to run a trial
Operationally
valid and feasible pro
tocol
Motivated, high
quality investigator
and site personnel
© 2016 INC Research Holdings, Inc.
Motivated,
informed protocol e
ligible patients
11
Driving connectivity in
clinical research
Lead with the best
Focus on the
clinical and
patient
operational science –
experience –
drive interface
collaborate with
between clinical goals
patient advocacy
and operational
Partner with
quality and
experienced sites
Driving
– support
connectivity
excellence
through
complexity
Convergence of patients/advocacy – specialized sites – scientific experts
Accelerated medicine development and patient access to therapy
© 2015 INC Research, LLC
12
Operational Challenges & Solutions
Scarce and dispersed population
•Site selection driven by patient geographic distribution and strategy
•Collaboration with patients’ associations and specialized networks
•Support of available and current registries
•Collaboratio with genetic or specialty laboratories
•Engagement of sites of excellence for specific rare diseases
Study start-up considerations
•Accurate sample size assumptions and rationale
•Endpoint selection and clinical assessments in new indications
•Appropirate Informed consent/assent in pediatric population
•Site selection strategy
•National Coordinator responsibilities
Investigational Site issues
•Inexperience sites might require training plan for GCP compliance
•Provide study sites with adequate operational support
•High intensity data review plan to ensure quality data quality, adequate follow-up
of early withdrawals
13
Focus on the patient
Take a patient centered approach
Partner with quality sites
• Early engagement in clinical development cycle
• Enable sites to focus on patient experience
• Collaborate with advocacy groups
• Provide operational support
• Ensure patient needs and concerns captured
• Ensure quality despite complexity
in the clinical protocols and development
plans
• Partner to raise awareness of clinical trials as
access to medicine
© 2015 INC Research, LLC
14
Solution to recruitment and retention
challenges
Focus on the patient experience
Enable sites to cater to patient needs
Patient Associations and
Genetic / Speciatly
Medical and Clinical
Informed Consent/Assent
Site Advocacy Groups
Testing Laboratories
Experts
Training
Special issues with travel
Minimize burdensome
Site support and training
logistics - support
site visits – Maximize
through for high
patients and caregivers
home nurse support
intensity visits
© 2014 INC Research, LLC
Disease and patient
specific recruitment plan
15
Collaboration with Patient
Advocacy Groups
• Support and cooperation critical to study
success
Patient
Advocacy
Groups
•
KOLs and
site PIs
Patients
and
Families
Sponsor
Patient
and CRO
Value
A Patient’s Advocacy Lead can facilitate interations with the advocacy fostering a partnership
model for delivery of the clinical program. Ensures advocacy group:
– Protocol input, review, and finalization to ensure inclusion of patient considerations
– Support for sites engagement and cooperation
– Endorsement of multi-channel outreach (web-based platforms, email, messages and other
communication mechanisms) to promote study awareness and participation
– Facilitation of connecting potential patients with the selected investigational sites
– Support for logistic management of patients to facilitate access to the study
– Education for patients, parents and community about the specific rare disease manifestati
on, progression and quality of life with the rare disease
© 2015 INC Research, LLC
16
Case Study: Spinal Muscle Atrophy (SMA) Foundation
Early engagement
•Started from study planning – fundamental considering the disease characteristics
•Ensured study design considered:
•Co-morbidities including frequent respiratory illnesses
•Intercountry variation in incidence, natural history, and survival
•Center to Center differences in Standard of Care
Close cooperation for patient recruitment and retention
•Provided valuable insights and understanding of the disease, SOC, patients/parent behaviors, and other factors impacting
willingness to participate.
•Facilitated family support
•Socialized trial awareness
•Facilitated patient access to the study
Inclusion in mutlidisciplinary team with patients, families, sponsor and the CRO
•Resulted in presentation of study results by CRO/sponsor to an SMA family gathering sponsored by the Spanish SMA
advocacy group and foundation, FUNDAME.
17
Partner with quality sites
• Overcome operational barriers
• Address within protocol
• Complexity of investigational product
• Cell based therapy, gene editing
• Storage and administration issues
• Complexity of laboratory assessments
• Specialty labs and special handling
• Intensity of screening and visit days
• May require staff augmentation
• Focus on recruitment AND retention
• May require additional support (on si
te and in the field)
Gap analysis and
Focus on quality,
support
trusted sites, with
implementation
access to patients
Acknowledge
Assess operational
operational
capabilities against
capabilities and
study requirements
limitations of
individual sites
© 2015 INC Research, LLC
18
Drive collaboration
• Peer to peer relationships ensure right patient
for best protocol
Treating
Physicians
Sponsor
CRO physicians
Site
Physicians
and scientists
Investiga-tors
• Leverages shared training and passion for the patients a
nd disease
• Ensures multiple clinical perspectives represented in prot
ocol design
• Drives connectivity between the sponsor and the investi
gational sites, surfacing operational issues early
• Allows timely review of emerging data so that any proto
col adjustments can be made in a nimble fashion
• Facilitates insight sharing from cross sponsor clinical res
earch
• Advances clinical research critical to developing treatmen
ts for these underserved diseases.
Academic
Thought
Leaders
© 2015 INC Research, LLC
19
Collaborative approach for Huntington’s Disease
• Coordination of all stakeholders and
collaborative planning
Sponsor
Companies
Caregivers
Patients
Families
Clinical
Research
Organizations
The International
Huntington Association
© 2015 INC Research, LLC
20
INC Rare Disease Consortium
A patient centered approach, underpin
ned by strong medical, operational, and
regulatory science and driven by collabor
ative relationships between investigative
sites, treating physicians, patient advocac
y groups, academic thought leaders, and
sponsor companies, drives the best pati
ent experience and the most robust cli
nical data.
21
Summary
•
•
•
•
•
Clinical development and research in rare diseases is challenging, difficult,
and rewarding work.
Success requires collaboration across many different stakeholders with
broad needs and priorities
Patient centered research approaches are critical to ensure the voice of
the patient is incorporated in both the scientific design and the
operational execution of clinical trials
Recognizing the tactical complexities for investigational sites participating
in these trials and devising solutions to optimize patient participation and
retention as well as data quality is tantamount
Clinical Research Organizations often sit in the center of these issues and
can provide insight and drive innovation and collaboration to achieve our
collective mission to improve the health of those suffering from rare
diseases.
© 2015 INC Research, LLC
22