Download Patients as Partners in the Development and Interpretation

Patients as Partners in the Development and
Interpretation of Clinical Outcome Assessments:
Methods, Challenges and Benefits
Milena D. Anatchkova, PhD, Research Scientist, Evidera; Lexington, MA
Theresa M. Mullin, PhD, Director, Office of Strategic Programs, FDA Center for Drug Evaluation and Research,
Silver Spring, MD
Linda S. Deal, MSc, Senior Director Head of Patient-Centered Outcomes Measurement, Pfizer, Collegeville, PA
Alice Bast, CEO, Beyond Celiac, Ambler, PA
© 2016 Evidera. All Rights Reserved.
Workshop Purpose

This workshop will discuss approaches to engagement of patients in
clinical outcomes assessment (COA) development, implementation,
interpretation, and dissemination in health care research

Patient engagement will be explored from multiple perspectives,
including:
– Food and Drug Administration (FDA)
– Pharmaceutical Industry
– Health Care Consulting
– Patient Advocacy Group
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1
Agenda

Theresa Mullin will present the current FDA initiative for obtaining
patient’s perspective on disease experience and treatment, and plans
for guidance on methodologically sound pragmatic approaches to
incorporating the patient’s perspective

Linda Deal will discuss sponsor organizations’ strategies to facilitate
patient engagement as research advisors, in contrast with seeking
their input in standard endpoint development research

Milena Anatchkova will describe patient engagement on collaborative
projects that include industry, patient advocacy groups, and academia

Alice Bast will report on a recent celiac disease research summit that
brought together patients and other key stakeholders to establish a
long-term patient-centered research agenda

You will provide your insights and perspectives on this important
issue
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FDA’s Initiative on
Patient-Focused Drug Development
Theresa M Mullin, PhD
Director, Office of Strategic Programs
FDA CDER
ISPOR Annual International Meeting
May 25, 2016
2
Patient-Focused Drug Development
under PDUFA V
• FDA began developing a more systematic way of gathering
patient perspective on their condition and available
treatment options
– Patient perspective helps inform our understanding of the context for
the assessment of benefit-risk and decision making for new drugs
• Patient-Focused Drug Development is part of FDA
commitments under the fifth authorization of the Prescription
Drug User Fee Act (PDUFA V)
– 20 meetings, each focused on a specific disease area, during PDUFA V
– Each meeting results in a Voice of the Patient report that faithfully
captures patient input from the various information streams
5
Patient Perspective Informs
Drug Benefit-Risk Assessment
Benefit-Risk Summary and Assessment
Dimension
Analysis of
Condition
Current Treatment
Options
Benefit
Risk
Risk Management
Evidence and Uncertainties
Conclusions and Reasons
Patient Focused Drug Development
Provides the therapeutic context
for weighing benefits and risks
Clinical Outcome Assessments (e.g., PROs)
Incorporates expert judgments
about the evidence of efficacy and
safety, and efforts to further
understand or mitigate risk
CDER – Office of Strategic Programs (OSP)
6
3
PFDD Meetings FY 2013-2017
Plan to complete 24 meetings during PDUFA V
Fiscal Year 2013
•
Fiscal Year 2014
Chronic fatigue •
syndrome/
•
myalgic
encephalomye •
litis
Sickle cell disease
•
HIV
•
•
Lung cancer
Inborn errors of
metabolism
•
Narcolepsy
•
Hemophilia A, B, and
other heritable
bleeding disorders
•
Fibromyalgia
Pulmonary arterial
hypertension
Idiopathic pulmonary
fibrosis
Fiscal Year 2015
•
Female sexual
dysfunction
•
Breast cancer
•
Chagas disease
•
Functional
gastrointestinal
disorders
•
Parkinson’s disease and
Huntington’s disease
•
Alpha-1 antitrypsin
deficiency
Fiscal Year 2016-2017
•
Non-tuberculous
mycobacterial lung
infections
•
Psoriasis
•
Neuropathic pain
associated with
peripheral neuropathy
(June 10th)
To be announced
•
•
•
•
•
Alopecia areata
Autism
Hereditary
angioedema
Patients who have
received an organ
transplant
Sarcopenia
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Questions asked
Burden of disease
•
Of all the symptoms that you experience because of your condition, which 1-3 symptoms
have the most significant impact on your life?
•
Are there specific activities that are important to you but that you cannot do at all or as fully
as you would like because of your condition?
•
How has your condition and its symptoms changed over time?
•
What worries you most about your condition?
Burden of treatment
•
What are you currently doing to help treat your condition or its symptoms?
•
How well does your current treatment regimen treat the most significant symptoms of your
disease?
•
What are the most significant downsides to your current treatments, and how do they
affect your daily life?
•
Assuming there is no complete cure for your condition, what specific things would you look
for in an ideal treatment for your condition?
8
4
Voice of the Patient Reports
• Each meeting results in a summary report that captures the
input from the various information streams
– Faithfully summarizes participants’ experiences and perspectives, in
their own voices
– May include a sample of the B-R Framework’s first two rows,
incorporating meeting input
• Input could support other aspects of drug development, e.g.
– Help identify areas of unmet need
– Develop clinical outcome tools (PROs, etc.) that better address patient
needs
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Learnings and Stakeholder input
Key Learnings
 Patients with chronic serious disease are experts on what it’s like to
live with their condition
 Patients want to be as active as possible in the work to develop and
evaluate new treatments
 Their “chief complaints” may not be factored explicitly into drug
development plans (as endpoints and measures of drug benefit
planned in trials)
• PFDD was intended to elicit broader patient input for a disease to
better inform clinical context of BR assessment—What’s next?
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5
Learnings and Stakeholder input
Stakeholders have told us
• Are not expecting FDA to address all current gaps in patient
engagement but want FDA to provide clear actionable guidance on
what they and others need to do
• Are concerned that many efforts underway may be duplicative and
not coordinated
• Are willing to participate in clinical trials but want them designed to
make that more feasible, sustainable, tolerable
• Want FDA to review and discuss PROs in development—early and
often—FDA currently has rather limited staffing with this focus and
expertise
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PFDD Next Steps
• Engage wider community to discuss methodologically
sound approaches that:
• Bridge from initial PFDD meetings to more systematic collection
of patients’ input
• Generate meaningful input on patients’ experiences and
perspectives to inform drug development and B-R assessment
• Are “fit for purpose” in drug development and regulatory
context
• Provide guidance
– For patient communities, researchers, and drug developers
– On pragmatic and methodologically sound strategies, pathways,
and methods to gather and use patient input
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6
Further integrating patient perspective
into drug development and decision making
What impacts
(burden of
disease and
burden of
treatment)
matter most to
patients and
how to measure
them?
What aspects of
clinical trials can be
better tailored to
meet the patients
who (might)
participate in the
trial?
Translational
Clinical Studies
How to better
integrate
patient reported
outcome data or
elicited patient
preferences into
Benefit-Risk
(BR)
assessments?
Pre-market review
How to best
communicate
the
information
to patients
and
prescribers?
Post-market
Need to build in Patients’ perspective starting in the Translational phase
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What methods and approaches
might be helpful to address in guidance?
• Collecting comprehensive patient community input on
burden of disease and current therapy
• Development of holistic set of impacts (e.g., burden of
disease and burden of treatment) most important to
patients
• Identifying and developing good measures for the
identified set of impacts that can then be used in clinical
trials.
• Incorporating measures (COAs) into endpoints considered
significantly robust for regulatory decision making
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7
Patient-Centricity
ISPOR May 25, 2016
Washington DC
Linda S. Deal, Sr. Director
Pfizer
Patient-Centered Outcomes Assessment (PCOA)
Personal Disclosure
Linda S. Deal
 is an employee of Pfizer and is a shareholder of Pfizer.

has shareholdings in other pharmaceutical companies through stocks
and mutual funds.

is a member of Beyond Celiac Board of Directors.

expresses opinions within this presentation that are hers and are not
necessarily those of Pfizer or ISPOR.
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What does it mean to be patient-centric?

Patient-Centric – Merriam Webster
1. Located in or at the center: central <a centric point>
2. Concentrated about or directed to a center <a centric activity>
– Attributive adjective – modifies a noun e.g. patient-centric drug development
– Nominal adjective – acts as a noun

Patient-Focused - Merriam Webster , also an adjective but targeted
1.
2.



(of a person or their eyes) adapt to the prevailing level light and become able
to see clearly
paying a particular attention to e.g. to the patient
I think we mean both! – concentrated about the patient while paying
particular attention to the patient
Patient Voice could be patient or caregiver/parent
Patient vs Patient Advocacy Group – caution
– Special interests
– Particular agenda
Multiple Options and Opportunities to
Hear the Patient Voice
Past
Future

Patient – perspective filtered through a Health Care Professional

Trial Research Subject – aggregated experience in a clinical trial,
an experimental unit

Qualitative Research Participant – expert on their individual
experience with a condition and desired outcomes from treatment

Research Partner – advisor on the feasibility of study designs,
procedures and schedule of events

Regulatory Partner – testimonials at Advisory Committee meeting

Outcomes Interpreter and Value Decision Maker
– Risk-benefit tradeoffs that are acceptable
– Value of and/or willingness to pay for a benefit
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A New Era of Patient Empowerment
Dr. Janet Woodcock:
• "It turns out that what is really bothering the
patient and what is really bothering the doctor
can be radically different things….patients are
true experts in their disease”.
• “It's clear you have to start with an
understanding of the impact of the disease on
the people who have it, and what they value
most in terms of alleviation before you set up a
measurement and go forward with truly patientfocused drug development."
PDUFA V Clinical Outcome Assessments Public Workshop, April 1, 2015
The Patient Journey
How can a new therapeutic favorably disrupt this journey?
Detection
Diagnosis
Signs &
Symptoms
Treatment
Coping
Death

Characterizes the sequence of events from the point of detection that
something is not right (illness), through diagnosis, signs and symptoms,
treatment, coping, and eventually death

Provides a directional guide to defining patient relevant and meaningful
treatment benefit
– However, the evidence required to support the concepts of treatment benefit requires
documenting the methodological approach put forth in the FDA PRO guidance (FDA, 2009)

Uncovers unmet need

While literature and HCPs can contribute to the sketch of this journey, the
patient experience is best captured directly from the patients!
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Identifying What Matters to Patients

Defining treatment benefit from the patient’s perspective
– the impact of a therapeutic intervention on how the patient survives feels or
functions

Methods for eliciting treatment benefits concepts that are
–
–
–
–
Relevant
Meaningful
Comprehensive
Complete
to patients
 Sources of patient voice – patients as
– Qualitative research participants
– Research partners as members of an advisory panel
– Patients whose voice is filtered through a Clinical Advisor
From Trial Subject to Trial Participant
 Engage and facilitate improved communication
– Informed consent forms written in plain language describing what
is being agreed and why it’s important
•
•
•
•
Procedures to be performed
Randomization and control arms
Adherence with taking study medication as described
Compliance in completing assessments according to instruction
– Use of technology to engage the participant between study visits
– Debrief trial participants at the end of the study about
• their experience
• Anything they’d like to share that wasn’t systematically or prospectively
captured
– Share results back with the trial participants
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What makes for a Good Patient Research
Partner or advisor?

Pharma commitment to educating patient communities about goals and
intentions of a clinical trial, including
–
–
–
–
–
–

Informed consent
IRB/EC review process
Trial design
Procedures
Outcomes to be assessed
Results and interpretation
Recognizing the patient that is insightful and able to express their
perspective well
– Qualitative research participants who demonstrate this can be re consented to
expand their role to research partner/advisor

Consideration of whether the patient is representing an unbiased view
– Drawing upon personal experience as a someone with the condition of interest
– Not representing the agenda or interests of a patient advocacy group
How Patient-Centric Are We as an Industry?
The Corporate Reputation of Pharma – The Patient Perspective in 2015 (US Edition), Feedback from 106 patient groups,
The Patient View, Understanding Patients, PUBLISHED March 2016
12
How Patient-Centric Are We as an Industry?
The Corporate Reputation of Pharma – The Patient Perspective in 2015 (US Edition), Feedback from 106 patient groups, The Patient View, Understanding Patients, PUBLISHED March 2016
How Patient-Centric Are We as an Industry?
The Corporate Reputation of Pharma – The Patient Perspective in 2015 (US Edition), Feedback from 106 patient groups,
The Patient View, Understanding Patients, PUBLISHED March 2016
13
Conclusions and Recommendations






We really want to be both patient-centric and patient-focused.
Merit in understanding the patient journey to initiate exploration of
treatment benefit from the patient perspective
Patients can, have and will serve increasingly important roles in drug
development, approval and access
Pharma can support and encourage those roles by investing in
engaging and educating patients and patient groups on the drug
development and regulatory requirements
With experience Sponsors will recognize characteristics of good
patient and patient group partners and advisors
GET ON BOARD! – This has become a real metric that is being
tracked in the Industry.
Patients Engagement in Clinical Outcomes
Assessment Research and Development
Milena D. Anatchkova, PhD, Research Scientist, Evidera; Lexington, MA
ISPOR Annual International Meeting
May 25, 2016
© 2016 Evidera. All Rights Reserved.
14
Background

There is increasing interest in engaging patients in all aspects of
health research, and in the use of information from COAs in clinical
practice, drug development, reimbursement decisions, and health care
performance evaluations

Patients are key stakeholders whose involvement in COA development
as research participants has been acknowledged as good scientific
practice

Recently, however, the perspective has shifted towards broader
patient engagement in all aspects of health research
29
Patient-Centered Health Care
Medical Model
Patient-Centered Model
Patient’s role is passive
(Patient is quiet)
Patient’s role is active
(Patient asks questions)
Patient is the recipient of treatment
Patient is a partner in the treatment plan
(Patient asks about options)
Physician dominates the conversation
(Does not offer options)
Physician collaborates with the patient
(Offers options; discusses pros & cons)
Care is disease-centered
(Disease is the focus of daily activities)
Care is quality of life centered
(The patient focuses on family & other activities)
Physician does most of the talking
Physician listens more & talks less
Patient may or may not adhere to treatment
plan
Patient is more likely to adhere to treatment plan
(Treatment accommodates patient’s culture & values)
Figure adapted from: Rees D. 2011 http://instructionaldesignfusions.wordpress.com/2011/03/10/patient-centered-care/
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15
How Has the Patient-centered Health Care Model
Impacted Health Care Research and Development?
Figure from EUPATI: http://www.patientsacademy.eu/index.php/en/
31
Patient-centered Activities at Evidera

Evidera established a Patient Engagement Working Group

Engagement with professional organizations and initiatives
– ISPOR Patient Engagement Task Force
– PCORI
– Rare Disease Virtual Huddle

Collaborate with academic organizations on patient-centered projects and
programs

Working with our clients and their existing patient - partner relationships
to engage patients in the research process and ensure a reciprocal,
positive research experience

Engaging patient partners as advisors and co-researchers at early stages
in the research process, providing opportunities for patient-centered
innovation in research design

Generating new patient-driven research questions
32
16
How Do We Engage Patient Partners Specifically in
COA Research and Development?
Research
Design
Data Collection
Formulate/fine-tune the
research question
Facilitate recruitment
Create early conceptual
framework
Patient liaison
Design interview guides
Post research questions in
online communities that
they belong to, with
appropriate disclosures
Data Analysis/
Interpretation
Obtain feedback on
conceptual models,
conceptual frameworks
created based on
interviews
Input on interpretation of
results
Input on presentation of
results
Review study protocols
Provide feedback on how
their participation in the
research helped
Design recruitment
strategies
Dissemination
Post research in online
communities
Share research findings at
patient conferences or
community meetings
Input on dissemination
materials
Participation in meetings
with regulatory and HTA
agencies when COA
discussed
Provide insight regarding
potential ethical dilemmas
that researchers without
the disease may not
foresee
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Evidera Patient Engagement Case Studies
Project Area
Partner
Patient Engagement
Evidera Role
• Critical and unique
sources of information
identified by the patient
consultant
• Consultant
Chronic
Disease
• Discussions with team
Pharma
• Feedback on concepts
• Recommended sources
of information
• Advisor
Rare Disease
Pharma/Patient
Advocacy
Organization
• Input on protocol
development
• Facilitation with patient
recruitment
Highlights
Proposed patient
engagement to
client, established
contact and
managed
relationship,
integrated input in
study report
• Importance of webresources for patients
highlighted
• Patient advisor identified
critical wording changes
in study material
• Recommendations for
wording changes
Quality of
Care
Academia
• Participants on study
stakeholder advisory
panel
• Quarterly panel
meetings and at key
milestones as needed
Evidera staff on
study stakeholder
advisory panel
• Patient stakeholders
helped formulate the
research question
• Helped with securing
study funding
• Provided detailed input
on study design materials
34
17
Patient-centered Value Model Rubric (NHC)
1. Patient Partnership. Patients should be involved in every step of the value
model development and dissemination process.
2. Transparency to Patients. The assumptions and inputs into the value
model itself – and each step in the process – should be disclosed to
patients in an understandable way and in a timely fashion.
3. Inclusiveness of Patients. The value model should reflect perspectives
drawn from a broad range of stakeholders, including the patient community.
4. Diversity of Patients/Populations. The value model should account for
differences across patient subpopulations, trajectory of disease, and stage
of a patient’s life.
5. Outcomes Patients Care About. The outcomes integrated into the value
model should include those that patients have identified as important.
6. Patient-Centered Data Sources.
35
Practical Implications of Engaging Patient Partners

Selection of patient partner
– How many?
– Does background matter?

Logistical
– Travel and/or meetings of long duration may be difficult for patient partners with
active chronic disease
– Discontinued participation due to condition exacerbation

Ethical and legal challenges
– Contracting
– Conflicts of interest
36
18
Conclusions

Projects with patient engagement are still more the exception than the
rule in consulting projects

Forms of patient engagement are very diverse

Project with patient engagement require careful planning and careful
attention to logistics

Further exploration of web based sources of information and patient
engagement need to be explored

Benefits of patient engagement are unique for each project
37
Forging Pathways to a Cure:
A Roadmap to Accelerating Progress for Patients
Alice Bast, CEO, Beyond Celiac
International Society for Pharmacoeconomics and Outcomes Research (ISPOR)
May 25, 2016
© 2016 Beyond Celiac
19
Beyond Celiac: A Brief History
2003
2004
2004
2013
2013
39
• Established the National Foundation for Celiac Awareness to immediately
drive diagnosis from a mere 3% and help people access the only medicine
available for celiac disease: gluten-free food
• Ultimate goal to support research and find a cure
• The first CeD patient organization to use digital and social media to
connect and build a trusted relationship with patient community
• Developed and implemented patient-focused programming to empower,
educate and engage patients
2014
2015
• Identified leading barrier: gluten-free diet overshadows celiac disease
• Implemented a formal strategic planning process and a Research Summit
to establish a patient-centered research agenda
2016
2016
• Unveiled a new name and brand in December 2015
• Beyond Celiac advances widespread understanding of celiac disease as a
serious genetic autoimmune condition and works to secure early diagnosis
and effective management
© 2016 Beyond Celiac
www.BeyondCeliac.org
2004 NIH Consensus Development Conference
on Celiac Disease
Consultation with a skilled dietitian
Education about the disease
Lifelong adherence to a gluten-free
diet
Identification and treatment of
nutritional deficiencies
Access to an advocacy group
Continuous long-term follow-up by a
multi-disciplinary team
40
© 2016 Beyond Celiac
www.BeyondCeliac.org
20
Why a Patient-Centered CeD Research Agenda is Needed
February 8, 2016
57% sometimes
get concerned or
embarrassed
about eating in
front of other
people
44% estimate
getting
(accidentally)
glutened at
least once a
month
Beyond Celiac survey results, October 2015, n =1,484
41
© 2016 Beyond Celiac
www.BeyondCeliac.org
Establishing a Patient-Centered Research Agenda:
The Beyond Celiac Process
Processes
Primary Research (2014)
Gaps Analysis (2014)
Participants
•
•
•
•
•
Leading Knowledge
Gaps
>150 diagnosed patients
and untested genetically atrisk relatives
•
7 international experts
2 patients
1 spouse of a patient
1 caregiver
•
•
•
•
•
Research Summit (2015)
42
•
51 multi-disciplinary
participants and experts,
including 22
patients/caregivers
•
Not recognized as a serious
condition
Gluten-free diet is a barrier
Burden of disease is not
quantified
No outcome measures
accepted by FDA
Myth that gluten-free diet is
“cure”
Underestimated market for
new treatments
Existing PRO measures or
resource utilization
measures are not
satisfactory
© 2016 Beyond Celiac
www.BeyondCeliac.org
21
Stakeholder Mapping:
A Network of Multi-disciplinary Experts
1
9
22
NIDDK
rep.
CeD
clinicians,
researchers
People living
with or affected
by CeD
10
Biotech
and pharma
companies
1
Diagnostics
company
51
Participants
ZERO
6
Researchers
(autoimmune
diseases,
computational
genomics,
biomedical
informatics, HEOR)
43
1
4
third party
payers
journalist
Other
patient
orgs.
© 2016 Beyond Celiac
www.BeyondCeliac.org
Amplifying the Patient’s Voice
Participation from 22 people living with or affected by CeD
2
members of our
Patient and
Family Advisory
Council
14
people with
clinical and/or
research
experience
4
members of
broader
community
2
members of our
Board of
Directors
5
staff
Criteria for participation:
• Newly diagnosed
• Long-term diagnosed, “veteran” patient
• “Average” patient
• Caregiver experience
• Established understanding of research
• Connected to social media community
• Experience in other countries
• Deep experience in a specific area
44
© 2016 Beyond Celiac
www.BeyondCeliac.org
22
The Research Summit:
3 Working Sessions - A Thoughtful, Strategic Process
45
© 2016 Beyond Celiac
www.BeyondCeliac.org
The Vision and Plan:
A Patient-Centered Approach to Collecting Data
Step 1:
Community Engagement Platform
Engage, educate and empower the
CeD community
Accelerate disease education and
management process
Capture collective experiences, both
qualitative and quantitative data
Build a knowledge base about:
• How CeD develops, is diagnosed
and managed
• Health economic implications of
CeD
• Mental, physical and emotional
impacts of CeD
Generate new research hypotheses
46
Step 2:
Patient Registry
Invite a demographically representative
group of Platform participants to join
Registry
Collect quantitative data necessary for
reliable PROs that measure disease
burden
Profile each participant in a HIPAA
compliant and searchable research
database
Enable research studies to:
• Analyze data from the database
• Evaluate PRO measures that can be
used for clinical trials
• Connect investigators with the right
study participants
© 2016 Beyond Celiac
www.BeyondCeliac.org
23
The Patient’s Role in Designing Research Tools:
What’s in it for me?
12-member Core Work Team with overlapping patient and professional
expertise
6
people
diagnosed
with CeD
•
•
47
1
mother of 2
children
with CeD
6
researchers/
clinicians
2
psychologists
1
blogger
1
PRO expert
Divided members into 4 teams:
– Partnered patients with professionals
– Project leaders who oversaw the process were 1 patient advocacy
professional and 1 biopharma/registry consultant
Between June and August 2015, the team reduced the number of questions
by 30%
© 2016 Beyond Celiac
www.BeyondCeliac.org
One Year Later: Where are we now?
Accelerating solutions and continuing patient engagement:
– Facilitated a partnership between Takeda Pharmaceutical Company and Cour
Pharmaceutical Development Company
– Relationship maintenance requires time, attention and strategy
Selecting the best technology partner:
• Six person ad hoc technology review committee, with two members of our Patient
and Family Advisory Council
• 18 other Council members invited to participate in demo calls and ”score”
vendors
Setting up for successful engagement and participation in research tools:
• Improve how we share medical, science and research news
• Increase participation in Beyond Celiac Research Opt-In, a community which is
specifically interested in clinical trials, surveys and other research studies
48
© 2016 Beyond Celiac
www.BeyondCeliac.org
24