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Partnering With Patients in the Development and Lifecycle of Medicines: A Call for Action

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The purpose of medicines is to improve patients’ lives. Stakeholders involved in the development and lifecycle management of medicines agree that more effective patient involvement is needed to ensure that patient needs and priorities are identified and met. Despite the increasing number and scope of patient involvement initiatives, there is no accepted master framework for systematic patient involvement in industry-led medicines research and development, regulatory review, or market access decisions. Patient engagement is very productive in some indications, but inconsistent and fragmentary on a broader level. This often results in inefficient drug development, increasing evidence requirements, lack of patient-centered outcomes that address unmet medical needs and facilitate adherence, and consequently, lack of required therapeutic options and high costs to society and involved parties. Improved patient involvement can drive the development of innovative medicines that deliver more relevant and impactful patient outcomes and make medicine development faster, more efficient, and more productive. It can lead to better prioritization of early research; improved resource allocation; improved trial protocol designs that better reflect patient needs; and, by addressing potential barriers to patient participation, enhanced recruitment and retention. It may also improve trial conduct and lead to more focused, economically viable clinical trials. At launch and beyond, systematic patient involvement can also improve the ongoing benefit-risk assessment, ensure that public funds prioritize medicines of value to patients, and further the development of the medicine. Progress toward a universal framework for patient involvement requires a joint, precompetitive, and international approach by all stakeholders, working in true partnership to consolidate outputs from existing initiatives, identify gaps, and develop a comprehensive framework. It is essential that all stakeholders participate to drive adoption and implementation of the framework and to ensure that patients and their needs are embedded at the heart of medicines development and lifecycle management.
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Review Article
Partnering With Patients in the Development
and Lifecycle of Medicines: A Call for Action
Anton Hoos, MD
1
, James Anderson, MA, MBA
2
, Marc Boutin, JD
3
,
Lode Dewulf, MD, Dip Pharm Med, FFPM
4
, Jan Geissler, Dipl-Kfm
5
,
Graeme Johnston, LLB, IPFA
6
, Angelika Joos, MPharm
7
, Marilyn Metcalf, PhD
8
,
Jeanne Regnante, MS
9
, Ifeanyi Sargeant, DPhil
10
, Roslyn F. Schneider, MD, MSc
11
,
Veronica Todaro, MPH
12
, and Gervais Tougas, MD, CM
13
Abstract
The purpose of medicines is to improve patients’ lives. Stakeholders involved in the development and lifecycle management of
medicines agree that more effective patient involvement is needed to ensure that patient needs and priorities are identified and met.
Despite the increasing number and scope of patient involvement initiatives, there is no accepted master framework for systematic
patient involvement in industry-led medicines research and development, regulatory review, or market access decisions. Patient
engagement is very productive in some indications, but inconsistent and fragmentary on a broader level. This often results in
inefficient drug development, increasing evidence requirements, lack of patient-centered outcomes that address unmet medical
needs and facilitate adherence, and consequently, lack of required therapeutic options and high costs to society and involved parties.
Improved patient involvement can drive the development of innovative medicines that deliver more relevant and impactful patient
outcomes and make medicine development faster, more efficient, and more productive. It can lead to better prioritization of early
research; improved resource allocation; improved trial protocol designs that better reflect patient needs; and, by addressing
potential barriers to patient participation, enhanced recruitment and retention. It may also improve trial conduct and lead to more
focused, economically viable clinical trials. At launch and beyond, systematic patient involvement can also improve the ongoing
benefit-risk assessment, ensure that public funds prioritize medicines of value to patients, and further the development of the
medicine. Progress toward a universal framework for patient involvement requires a joint, precompetitive, and international
approach by all stakeholders, working in true partnership to consolidate outputs from existing initiatives, identify gaps, and develop a
comprehensive framework. It is essential that all stakeholders participate to drive adoption and implementation of the framework
and to ensure that patients and their needs are embedded at the heart of medicines development and lifecycle management.
Keywords
patient involvement, medicines development
Introduction: Problem Statement
Drug development times are around 10 to 15 years
1,2
and costs
to bring a single new therapy to market are substantial.
1-3
From
the industry perspective, not putting the unmet medical needs
of patients first, early in the development process, can lead to
wrong priorities, wrong decisions on research design, and
potentially costly late-stage failure. The complexity of clinical
trials may lead to long and difficult experiences for patients
4,5
and recruitment into clinical trials is ever more competitive and
increasingly problematic.
6
Many trials fail to achieve recruit-
ment targets because they may be too restrictive in terms of
exclusion/inclusion criteria, may impose an unfeasibly heavy
1
M4P (Medicines 4 Patients) Consulting, London, UK
2
GlaxoSmithKline, Brentford, Middlesex, UK
3
National Health Council, Washington, DC, USA
4
UCB Biopharma, Brussels, Belgium
5
European Patients’ Academy on Therapeutic Innovation, Brussels, Belgium
6
Chackmore, Buckinghamshire, UK
7
Global Regulatory Policy, MSD (Europe) Inc, Brussels, Belgium
8
Chief Medical Office, GlaxoSmithKline, Raleigh-Durham, NC, USA
9
Merck & Co Inc, Kenilworth, NJ, USA
10
Ismedica Ltd, Staffordshire, UK
11
Global Patient Affairs, Pfizer Inc, New York, NY, USA
12
Parkinson’s Disease Foundation/Clinical Trials Transformation Initiative,
New York, NY, USA
13
Chief Medical Office, Novartis Pharma AG, Basel, Switzerland
*
Anton Hoos is currently an employee of Amgen
Submitted 04-Feb-2015; accepted 11-Mar-2015
Corresponding Author:
Anton Hoos, MD, Amgen (Europe) GmbH, Dammstrasse23, Zug, 6300, Switzerland.
Email: ahoos@amgen.com
Therapeutic Innovation
& Regulatory Science
1-11
ªThe Author(s) 2015
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burden of visits and tests on the participant, or may lack essen-
tial elements such as crossover or adaptive design, causing
patients either not to enroll or to abandon a trial. Clinical or
contract research organizations tasked with operational aspects
of clinical trials are generally isolated from patients and
patients’ needs. Furthermore, trials may include comparator
or placebo groups or outcome measures that may not ade-
quately reflect patient priorities.
7-9
In every industry, product development begins with a clear
understanding of the needs of the end user and aims to provide
solutions that meet that need: the same should be true for med-
icines development. Although the purpose of medicines is to
improve patients’ lives and to provide more effective health
care, current patient involvement during medicines develop-
ment and lifecycle management is fragmentary at best, and
mostly confined to post-launch or late-stage clinical develop-
ment. Without a clearly defined, timely, and methodological
process, patient involvement will continue to be inconsistent
and suboptimal.
Patients and biopharmaceutical companies should forge
working collaborations that secure structured and integrated
patient involvement at all phases of the medicines lifecycle.
For this to happen in the real world, the value and benefits of
patient involvement—and conversely, the consequences of
failing to involve patients—need to be clear. This clarity,
alongside evidence of the positive impact of patient involve-
ment, will be a powerful driver for improvement.
Hypothesis: Routine Involvement of Patients
During the Development and Lifecycle of Medicines
Will Lead to Better Outcomes
Patients and their representatives can give valuable insights
over the entire medicines development pathway—from precli-
nical laboratory-based studies to launch, and beyond launch to
ultimate withdrawal from the market—for as long as that med-
icine is available to patients. Examples are in research scoping,
study designs, recruitment, safety monitoring, understanding,
and dissemination of research results (including lay summaries
for nonexperts) and in describing their experiences with the use
of medicines in settings outside of clinical trials.
Medicines are developed to improve patients’ lives and
patients know best what makes a meaningful difference to
them. Patients have a role to play alongside all other stake-
holders in determining intended outcomes and priorities,
acceptable uncertainty, as well as benefit/risk and value of a
medicine. Their recommendations and conclusions may be dif-
ferent from those of regulators, payers, academic researchers,
other health care professionals (HCPs), and industry,
10
making
it even more important that these opinions are well understood
by all those making decisions.
Improved patient involvement will inspire and drive the
development of innovative medicines that deliver more rele-
vant and impactful patient outcomes. Trials and protocols will
be designed to better reflect patient requirements and con-
ducted with greater consideration of patient circumstances,
allowing more patients to participate and potentially benefit
from these therapies while they are still being evaluated. It also
means that medicines entering the market are better able to
address the actual health needs of patients for whom there may
be inadequate or no specific treatments available.
Improved patient involvement has the potential to make
medicine development faster, more efficient, and more produc-
tive. It can facilitate improved coordination of the process, pre-
vent duplication of effort and inefficient resource use, and
inform the wider health policy decision-making process.
Although only few studies have attempted to measure the
impact of patient involvement, alongside anecdotal reports,
there is evidence in the literature to support these claims.
11-13
Serving patients requires a deep understanding of their med-
ical condition, especially in terms of the challenges they face in
everyday living, their goals, disease symptoms and side effects
of therapies, and unmet needs in terms of therapy and quality of
life. These insights can be gained only through direct and con-
structive interactions with patients. Once the needs are clearly
understood, all stakeholders—including industry, regulators,
patients, patient associations and advocacy groups, purchasers
of medicines (including pharmacies and hospitals), HCPs
including academic and community-based researchers, phy-
sicians and nurses, politicians and legal advisors, health
technology assessment (HTA) agencies, and topic-related
think-tanks—can work together to develop practical and imple-
mentable solutions and achieve more meaningful outcomes.
A Common Understanding Starts With
a Common Language
Selection of the term patient involvement rather than patient
empowerment or patient engagement is deliberate and inten-
tionally captures the central role that patients should play in
medicines development and lifecycle management. Involve-
ment reflects the need for patients to be active participants—
valued and valuable partners—whose input, advice, and gui-
dance is sought and implemented throughout the process.
Today, a lot of different terms are used, and often the same
terms are used while being differently defined or intended. This
adds to and maintains the confusion. Thus, a clear definition of
what is meant by patient and involvement, along with identifi-
cation of key stakeholders, is critical to achieve a common
understanding. First, the definition of patient needs to be wide
in order to capture all relevant populations who can provide
valuable insights through different lenses (Box 1). It should
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also be recognized that, as well as having keen insight and a
different perspective, caregivers may sometimes be trying to
lead 2 lives—their own and that dedicated to the patient. Sec-
ond, involvement should not stop with consultation but should
proactively embed patients and patient needs at the heart of
the development and lifecycle of medicines. Patients’ views
and opinions should be clearly sought and valued as an inte-
gral and essential part of the process, with the development
of strategies and practical tools that facilitate genuine patient
involvement.
There is already a substantial and growing number of
organizations and initiatives aiming to improve patient and
public involvement. This is evidence of the increasing rec-
ognition of patient involvement as a shared priority, and
many valuable contributions toward this common goal are
being made. However, there is as yet no consistent approach
or methodology. A master framework that identifies specific
stages in the development and lifecycle of medicines for
patient involvement, clearly defines the scale of this invol-
vement, and is agreed on by all stakeholders is essential and
currently lacking. Present initiatives are engaging patients in
discrete sections of the medicines development pathway,
and many of the elements and enablers for successful patient
involvement already exist. The need now is to develop a mas-
ter framework that unites these sections and closes gaps in the
pathway, providing much-needed guidance for productive and
consistent patient involvement.
Enablers and Examples of Patient Involvement
Health Literacy
Health literacy is defined as the degree to which individuals
have the capacity to obtain, process, and understand basic
health information and services needed to make appropriate
health decisions, and it can affect people of all ages, races,
incomes, and education.
14,15
It is universally accepted that
health literacy is a critical enabler to engage and involve
patients in their health care and the health of those who they
care for. There are many initiatives under way that are enabled
by health literacy concepts—which would better engage
patients in medicines development—including provision of
patient-focused materials at each stage of the medicines life-
cycle. Examples include improvement of informed consent,
return of results, and patient information guides or leaflets
(Box 2).
Expertise and Skills of Patient Advocacy Groups—
Access to Information for Every Patient
The Internet and digital media resources enable patients to
access almost unlimited information, to exchange experiences,
and to form opinions. As a result, the individual knowledge of
patients about their disease, related treatment options, and
ongoing research has grown exponentially.
16,17
Portals such
as www.patientslikeme.com allow an exchange of disease and
treatment experiences among patients and even offer tracking
Box 2. Examples of patient-focused materials.
Informed Consent: The Clinical Trials Transfor-
mation Initiative’s (CTTI’s) Informed Consent Proj-
ect aims to create and pilot a more effective
process, including appropriate materials, for ensur-
ing research participants’ understanding of critical
informed consent elements, taking into account
variability among research settings and participants
(http://www.ctti-clinicaltrials.org/what-we-do/
study-start-up/informed-consent).
Return of Results: The Multi-Regional Clinical
Trials Center (MRCT) at Harvard University
Return of Results Initiative aims to develop stan-
dards and best practices in returning clinical trial
results to study participants. The aim is to create
a guidance document, including templates, and to
address perceived barriers to widespread imple-
mentation (http://mrct.globalhealth.harvard.edu/
return-results).
Patient Information Guides and Leaflets:
Patients are often presented with an overwhelming
amount of information that is distributed in an
uncoordinated and inconsistent manner. In
response to this the FDA, the Engelberg Center for
Health Care Reform, and other stakeholders have
been developing a single, standardized Patient Medi-
cation Information (PMI) document which is now at
the implementation stage (http://www.brookings.
edu/events/2014/07/01-patient-medication-informa
tion-prescription-phrma-fda).
Box 1. Definition of patient.
Those having or at risk of having the medical condi-
tion(s) whether or not they currently receive med-
icines or vaccines to prevent or treat a disease—
the traditional definition of a patient.
The family and those caring for those with the med-
ical condition(s)—all of these people are in fact liv-
ing with the disease.
Hoos et al 3
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opportunities of the individual’s health parameters. Facebook,
Internet forums, and other social media platforms are used by
individuals and patient organizations to distribute information
instantly.
18
Global networks of patient organizations have
formed to collaborate with HCPs and, in some cases, industry
and to provide up-to-date information to the patient commu-
nity, independent of borders and languages. Industry also pro-
vides response to specific requests from patients through their
medical information departments. The informed, empowered
patient is becoming the norm.
EUPATI—Enabling and Educating Patients to Give
Meaningful Input Into Drug Development
Meaningful patient input into drug development and evaluation
requires not just information but specific knowledge—all sta-
keholders are asked to contribute toward this goal. A good
example is the European Patients’ Academy on Therapeutic
Innovation (EUPATI), a collaborative public-private partner-
ship project of 30 organizations that is funded by the Innovative
Medicines Initiative. It was formed to increase the number and
capabilities of patients and related organizations to advise on
drug development. The first ‘‘class’’ of 50 patients will ‘‘grad-
uate’’ from the EUPATI Patient Experts Training Course in
November 2015. The EUPATI will also develop an Internet-
based toolbox for patient advocates and a public Internet
library covering all aspects of preclinical development, clinical
trials, regulatory affairs, pharmacovigilance, benefit-risk
assessment, and HTA in lay language.
19
Clinical Trials Transformation Initiative—
Enhancing Patient Involvement in Clinical Trials
The Clinical Trials Transformation Initiative (CTTI) was estab-
lished by Duke University and the FDA as a public-private part-
nership in 2007 and brings together more than 70 organizations
including academic research organizations, patient groups,
industry, government, institutional review boards, and investi-
gators. Its aim is to improve the clinical trials enterprise through
identifying and promoting practices that will increase the quality
and efficiency of clinical trials and, consequently, enable reli-
able and timely access to evidence-based prevention and treat-
ment options. The CTTI’s Patient Leadership Council (PLC),
launched in January 2013, brought together 15 patient thought
leaders representing a variety of organizations engaged in clin-
ical trials across diverse indications. The PLC initiated the
CTTI’s Patient Groups and Clinical Trials project, which aims
to formulate recommendations and tools that establish and sup-
port best practices for effective engagement between research
sponsors and patient groups around clinical trials. The PLC also
focused on delivery of presentations and events highlighting
innovative programs and approaches by patient groups to over-
come barriers in clinical trials. Following the success of
partnership programs, PLC members have been integrated into
the CTTI’s Steering Committee (as of January 2015) and repre-
sentatives of the patient community now have leadership
responsibilities and representation equal to all other CTTI sta-
keholders. A key learning from the PLC has been that the
patient community must be equal partners in every aspect of
the clinical trial enterprise in order to improve the quality and
efficiency of clinical trials.
PCORI—Facilitating Informed Health Decision Making
Patients have unique perspectives that can change and improve
health care research by potentially enhancing relevance of out-
comes to actual health decisions, driving more rapid uptake of
research into practice, and improving the likelihood that
patients will achieve the health outcomes they desire.
20
The
Patient-Centered Outcomes Research Institute (PCORI) is a
nonprofit, nongovernmental organization that aims to improve
the quality and relevance of evidence available to help patients,
caregivers, clinicians, employers, insurers, and policy makers
make informed health decisions. The organization funds com-
parative clinical effectiveness research and supports work that
will improve the methods used to conduct such studies.
Patients are increasingly well-organized and patient organi-
zations offer many of the skills and capabilities needed for suc-
cessful drug development both on a disease-specific level and
for overarching topics. Their expertise and influence will lead
to more significant patient involvement in the future on health
policy, quality of care, the research agenda, and reimbursement
decisions. The impact that patient organizations can have is
well illustrated by advocacy groups focusing on a specific dis-
ease (Box 3), on a series of linked or similar diseases, or on uni-
versal health policy applicable to all diseases (Box 4). While
CFF and PDF are disease specific, there has also been an emer-
gence of competent and passionate patient organizations that
cover whole ranges of conditions (Box 4).
Both in Europe and the US, multistakeholder patient advo-
cacy organizations have accumulated a huge amount of knowl-
edge, and their expertise and influence at the systems level will
lead to further evolution.
Patient & Public Involvement in Research
The principle of patient and public involvement has been
embraced by many academic and governmental stakeholders
with the intent to develop treatments that better meet people’s
needs. Educated patient input into research planning, clinical
study design, conduct, interpretation, and dissemination is
expected to lead to outcomes more relevant to patients and to
higher health impact to the broader population of patients.
Patient and public involvement has been implemented in Eur-
ope, the United States, Canada, and Australia. For example, in
the UK, the National Institute for Health Research (NIHR) is
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part of the government’s strategy, ‘‘Best research for best health.’
The NIHR wants patients and the public to be involved in all stages
of research and, together with its partners—the UK Clinical
Research Collaboration and Involve—has put structures in place
to achieve and facilitate this.
23
A US organization that is aiming
at a multistakeholder approach to change the system is Faster-
Cures.
24
Their goal is ‘‘to save lives by speeding up and improving
the medical research system.’’ They realize that meaningful patient
involvement with all stakeholders is key to achieving this ambition.
Regulators Inviting Patient Input
In both the US and Europe, a range of schemes to facilitate
patient involvement in the regulatory process has been estab-
lished. In the US, the Prescription Drug User Fee Act (PDUFA)
aims to expedite the drug approval process and enhance patient
involvement in drug development. The FDA’s Patient Focused
Drug Development initiative is a commitment under the current
PDUFA V to obtain patients’ input on specific disease areas as
well as their conditions, impact on daily life, and available
therapies. Examples of diseases explored so far include hemo-
philia, lung cancer, and HIV, and at least 20 public meetings
will be held, each focused on a specific disease area.
25
The
FDA has recently requested input from stakeholders on strate-
gies to obtain the views of patients during the medical product
development process and ways to consider patients’ perspec-
tives during regulatory discussions.
26
Assessment of a product’s benefits and risks involves anal-
ysis of the severity of the condition alongside available treat-
ment options and is a critical aspect of the FDA’s decision
making as it establishes the context in which the regulatory
decision is made. Based on the belief that a more systematic
and comprehensive approach to obtaining the patient perspec-
tive on benefits and risk would improve the drug development
and review process, the FDA has developed a structured frame-
work for benefit-risk assessment in regulatory decision making
for human drug and biologic products. PDUFA V also includes
a commitment to implement this framework in the new drug
approval process and a 5-year plan has been produced that
describes the FDA’s approach for its further development and
implementation.
27
The plan will be refined and updated
throughout PDUFA V, which runs until 2017, incorporating
stakeholder feedback.
Box 3. Examples of disease-specific knowledge and
influence of patient organizations.
21,22
An early example of powerful patient involvement
in gaining access to much needed therapies is HIV.
In the 1980s HIV-infected patient advocacy groups
caused a re-assessment of how much evidence is
needed to gain access to potentially life-saving
therapies; their tolerance for uncertainty and risk
also led to a complete change of the licensing
approach of promising medicines for people with
HIV [21].
Cystic Fibrosis Foundation (CFF) expertise and
influence spans the entire life cycle of drug develop-
ment and commercialization. Among others, they
offer drug discovery and development collabora-
tion capabilities, as well as a network for clinical
research and care. In 2012, fundraising revenue
amounted to US$ 134 million while royalties
amounted to US$ 156 million. In addition, CFF’s
US$ 75 million investment into Vertex’ Kalydeco
contributed to its approval in 2012 [22].
The Parkinson’s Disease Foundation (PDF) Parkin-
son’s Advocates in Research (PAIR) program which
aims to drive development of better treatments at a
faster pace by ensuring that people with Parkinson’s
and care partners are primary partners in research
alongside scientists, industry and government. The
cornerstone of the PAIR program is a national net-
work of more than 200 Research Advocates who
complete a Learning Institute, during which they are
trained by leading experts from the field about the
science of Parkinson’s and the development of new
treatments. Research Advocates serve as FDA
patient advisors, are members of IRBs and Data
Safety Monitoring Boards, advise investigators on
study design and protocol and educate their peers
about the importance of study participation.
Box 4. Examples of overarching patient organiza-
tions and involvement.
The European Patients Forum (EPF), the European
Organisation for Rare Diseases (EURORDIS) and
the European AIDS Treatment Group (EATG) have
been active in promoting a patient-centred philoso-
phy and agenda within EU institutions. In the US, the
National Organization for Rare Disorders (NORD)
is also driving greater patient involvement.
The US National Health Council (NHC) brings
together all segments of the health community to
provide a united voice for the more than 133 mil-
lion people with chronic diseases and disabilities
and their family caregivers (NHC).
Hoos et al 5
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In Europe, the EMA also has multiple efforts ongoing to
enhance patient involvement, including in many of its commit-
tees. In addition, the EMA’s Patients’ and Consumers’ Work-
ing Party representatives are involved in many EU-wide
initiatives including the European Network of Paediatric
Research, the European Network of Centres for Pharmacoepi-
demiology and Pharmacovigilance, and the Pharmacoepide-
miological Research on Outcomes of Therapeutics
consortium.
28
As a consequence of these efforts, the EMA’s
interaction with patient and consumer organizations has shown
substantial growth in recent years (Figure 1).
The EMA has also developed and published terms of refer-
ence for the involvement of patients in benefit-risk discussion
and evaluation within its scientific committees, its working
parties, and scientific advisory groups.
30
The guidance aims
to ensure that involvement is consistent and efficient and pro-
vides advice on when patient involvement may be valuable,
defines expectations from patient involvement in benefit/risk
evaluation, and advises on appropriate processes for patient
engagement and consultation. In September 2014, the EMA
launched a pilot project to involve patients in the assessment
of the benefits and risks of medicines in its Committee for Med-
icinal Products for Human Use (CHMP). Patients have been
invited to present their views on medicines for which there is
an unmet medical need and where the CHMP has concerns.
Patients may also be invited to give their views in cases where
the CHMP is considering whether to recommend the with-
drawal, suspension, or revocation of a marketing authorization,
or a restriction of indication of an authorized medicine.
31
HTA Bodies and Payer Organizations
Health technology assessment agencies in several countries
have also focused on improving patient involvement and are
asking patients to engage at the time of reimbursement
decisions for payer decision making. Current examples are
listed (Table 1), although wide variation is seen between agen-
cies on how patient engagement is conducted and how much
impact it has on decisions. In addition, the overarching organi-
zation, Health Technology Assessment International, which
has members from 59 countries, has an Interest Sub-Group for
Patient and Citizen Involvement in HTA (PCISG). The PCISG
aims to promote and develop methodologies to incorporate
patients’ perspectives in HTAs, facilitate sharing of best prac-
tice in patient and citizen involvement in the HTA process, and
provide support for countries with limited experience of patient
and citizen engagement in HTA.
32
Legislation
The FDA’s Safety and Innovation Act, which reauthorized the
PDUFA, incorporates legislation that aims to increase patient
participation in medical product regulation. Section 1137 aims
to gain patient views during the medical product development
process and regulatory discussions, while section 907 evaluates
the inclusion of demographic subgroups in clinical trials.
33,34
The FDA has also developed guidance for industry on the col-
lection of race and ethnicity data in clinical trials.
35
An FDA
report reviewing the collection, analysis, and availability of
demographic subgroup data for FDA-approved medical prod-
ucts concluded that current statutes, regulations, and policies
provide a solid framework for product sponsors in their appli-
cations on the inclusion and analysis of demographic sub-
groups and that generally sponsors incorporate demographic
profiles and subset analyses in their applications.
36
EMA Pae-
diatric Regulation,
37
which came into force in January 2007,
has established patient representation at the Paediatric Com-
mittee. In addition, EMA legislation on pharmacovigilance,
which came into effect in July 2012, saw the establishment
of PRAC and a legal requirement for the engagement of
Figure 1. Growth of EMA interactions with patients and consumer
organizations between 2007 and 2013. Reproduced with permission
from European Medicines Agency.
29
Table 1. Countries engaging with patients during reimbursement
decisions for payer decision making.
Australia Pharmaceutical Benefits Advisory Committee
Canada Canadian Agency for Drugs and Technologies in
Health
England and
Wales
National Institute for Health and Care Excellence
France French National Authority for Health
Germany Institute for Quality and Efficiency in Healthcare as
well as Joint Federal Committee
New Zealand Pharmaceutical Management Agency
Scotland Scottish Medicines Consortium
Sweden Dental and Pharmaceutical Benefits Agency
The Netherlands National Health Care Institute (formerly College
voor zorgverzekeringen, Health Care Insurance
Board)
United States Patient-Centered Outcomes Research Institute
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patients and HCPs in the regulatory process, including direct
consumer reporting of suspected adverse drug events.
38
Potential Barriers to Patient Involvement
A number of reports have highlighted key issues in the involve-
ment of patients in the health care process, many of which have
also been identified in the setting of patient involvement in
medicines development. Examples of these perceived risks and
barriers are given (Table 2).
31,39-43
Ongoing and planned
patient involvement initiatives likely will identify additional
barriers and seek solutions to overcome them.
The above examples of initiatives that aim to secure patient
input demonstrate the substantial headway that is already being
made. However, the focus is too often on the expected medical
outcome, but a patient’s aspiration is the motivation to take the
journey to get to the desired medical outcomes. From the
patient perspective, the quality care trifecta includes not only
the medical outcome but also the journey to reach that outcome
and the individual’s personal aspirations—all 3 must be in bal-
ance (Box 5). By engaging with patients to capture and incor-
porate their wants and needs into the lifecycle of medicines,
industry will be more effective in developing and providing
treatments that help people on their journey to better health.
The Path to a Master Framework
for Integrated and Systematic Patient Involvement
The ultimate goal is to ensure that medicines deliver more rel-
evant and impactful patient outcomes by addressing unmet
patient needs, and medicine development is faster, more effi-
cient, and more productive through systematic patient involve-
ment. This can be accomplished only through open dialogue on
Table 2. Perceived risks and barriers to patient involvement.
Education and training Educational needs of stakeholders,
including scientific literacy
Lack of a common understanding of
what patient involvement entails
Need for training and guidance on
effective patient involvement
Communication Need for effective communication
with appropriate phrasing that is
understood by all stakeholders and
that reflects the diversity of the patient
population
No agreed on and comprehensive
definition of patient
Perceptions and
cultural barriers
Perception that patient involvement is
driven primarily by regulatory
concerns
Phenomenon of tokenism, where
patients are involved but their inputs
are not truly heard and acted upon
Perception of patient engagement as a
‘soft’’ science
Perception of engagement with
patients as risky
Need for a cultural shift to accept the
importance of patient engagement
Need to establish an environment of
mutual trust and respect, openness,
and reciprocity
Evidence Lack of robust evidence for the
benefits and value of patient
involvement
Structure, support,
and resources
Lack of a structured approach and
agreed on framework for patient
involvement
Logistics and support required to
ensure wide patient representation
Availability of resources to develop
and implement patient involvement
initiatives
Legal and regulatory Impact of legal and regulatory
restrictions on the industry’s and
other stakeholders’ communication
with patients
Box 5. Examples illustrating the need to balance
medical outcome with the medical journey and
individual aspirations.
A father with diabetes and heart disease wants to
follow his doctor’s orders to reach his desired
medical outcome to be in better health, but his
journey to reach that outcome is difficult to man-
age. He is a bus driver and the prescribed medica-
tions make him drowsy. This man’s aspiration is
to make sure he can work to provide a better life
for his children. It is only by prioritising this aspiration
and altering the journey by finding a treatment that will
allow him to keep working, that the patient can achieve
the desired medical outcome.
A single mother with breast cancer who has a child
diagnosed with autism and a parent with early signs
of dementia struggles to keep her family together.
Working part-time, she is emotionally underwater.
Her life aspiration is unclear. She lives in a rural
community eight hours away from an academic
medical centre and relies on the local community
health clinic and pharmacy chain for her care. Her
journey to better health may involve social services
to help her financially and to provide care for her
parent. It is by identifying quality measures that matter
to each unique patient that medical outcomes become
achievable.
Hoos et al 7
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a peer-to-peer basis with patient representatives and when a
rational, structured process for integrated patient involvement
is developed and accepted by all stakeholders. Systemwide
progress to achieve consistent patient involvement will require
stakeholders to work together on a noncompetitive basis. The
framework to deliver improved patient involvement will
benefit all partners, thus fostering cooperation rather than
competition. Development of the framework through equal
noncompetitive contribution is essential to ensure that the
framework is valid and accepted by all. Collaboration should
be across borders and regardless of affiliation in order to estab-
lish uniform standards that promote full and meaningful patient
involvement during the entire lifecycle of medicines. Many
groups have considered opportunities for patient involvement
during the development and registration of medicines, and a
good example from the US National Health Council is shown
in Figures 2 and 3.
This work provides a sound basis for further refinement;
a rational and synergistic approach would be to integrate
existing successful initiatives to drive development of a
master framework for patient engagement that covers the
entire medicines pathway. Key steps toward this end would
be to:
Map the medicine lifecycle and agree on essential and
optimal time points for patient engagement (a good
example from the CTTI is given in Figure 4)
Define goals of patient involvement at each time point/
period, specific activities and required outcomes, as well
as resource and capability needs
Figure 2. Patient engagement in the R&D process. Reproduced with permission from the National Health Council.
44
Figure 3. Patient engagement in regulatory decision making. Reproduced with permission from the National Health Council.
44
8Therapeutic Innovation & Regulatory Science
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Outline methods of engagement as well as current regu-
lations regarding interactions of patients with industry,
academic, regulatory, and community groups, and iden-
tify potential challenges
Map existing stakeholder initiatives to identify gaps,
avoid duplication, and improve synergies
Develop, disseminate, and drive implementation of the
master framework
A Call to Action
Patients and society need more effective, needs-based, and
targeted development of medicines and, once developed and
proven to show added value, rapid access to therapies that
meet their medical needs. Most stakeholders agree that more
effective patient involvement is essential in order to better
prioritize and drive rational, strategic medicines development
and lifecycle management.
45
Despite currently fragmentary
approaches, the plethora of schemes demonstrate widespread
acceptance of the value of constructive collaboration. Devel-
opment and validation of a master framework for systematic
patient involvement in industry-led medicines research and
development is the crucial next step to create better medicines
and better health.
There are fundamental success criteria that will need to be
met in order to successfully develop and establish a master
framework. Framework development should be driven by a
multinational partnership with balanced representation of sta-
keholders working together in line with agreed on principles
to ensure openness, inclusiveness, transparency, and credibil-
ity. The framework must be supported and endorsed by patient
organizations across diverse areas of illness, health, and policy;
the FDA, EMA, and other regulators; HTA bodies and payers
globally; medical and other relevant professional organiza-
tions; and a critical mass of biopharmaceutical companies.
We call all stakeholders in the medicine development chain
to collaborate, actively share outputs from existing initiatives,
and develop specific projects that will remove the current bar-
riers, build professional capacity on patient involvement in
industry and patient advocates through education and training,
and fill existing gaps in order to make continuous patient invol-
vement a reality. We are currently actively working toward
forming an open network to develop such a framework and
would urge stakeholders to contribute to and support its devel-
opment and adoption. A collaborative inclusive approach and
widespread implementation of the framework will help to
ensure that patients and their needs are embedded at the heart
of medicines development.
Acknowledgments
The authors thank Diana Hughes (affiliated with Pfizer Inc, New
York, at the time of manuscript preparation) for her valuable input
in the planning of this article.
Figure 4. Patient roles in the clinical trials continuum. Adapted from Parkinson’s Disease Foundation materials and developed by the Clinical
Trials Transformation Initiative. Reproduced with permission from the Parkinson’s Disease Foundation.
Hoos et al 9
by guest on July 7, 2015dij.sagepub.comDownloaded from
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest
with respect to the research, authorship, and/or publication of this
article. The following authors are employees of GlaxoSmithKline
(J.A., M.M.); UCB Biopharma (L.D.); MSD (Europe) Inc (A.J.);
Merck & Co, Inc (J.R.); Pfizer Inc (R.F.S.); and Novartis Pharma
AG (G.T.). The opinions expressed in this article are those of the
authors and do not necessarily reflect the views of their employers
or organizations.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
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Background: Health services have traditionally been developed to focus on specific diseases or medical specialties. Involving consumers as partners in planning, delivering and evaluating health services may lead to services that are person-centred and so better able to meet the needs of and provide care for individuals. Globally, governments recommend consumer involvement in healthcare decision-making at the systems level, as a strategy for promoting person-centred health services. However, the effects of this 'working in partnership' approach to healthcare decision-making are unclear. Working in partnership is defined here as collaborative relationships between at least one consumer and health provider, meeting jointly and regularly in formal group formats, to equally contribute to and collaborate on health service-related decision-making in real time. In this review, the terms 'consumer' and 'health provider' refer to partnership participants, and 'health service user' and 'health service provider' refer to trial participants. This review of effects of partnership interventions was undertaken concurrently with a Cochrane Qualitative Evidence Synthesis (QES) entitled Consumers and health providers working in partnership for the promotion of person-centred health services: a co-produced qualitative evidence synthesis. Objectives: To assess the effects of consumers and health providers working in partnership, as an intervention to promote person-centred health services. Search methods: We searched the CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL databases from 2000 to April 2019; PROQUEST Dissertations and Theses Global from 2016 to April 2019; and grey literature and online trial registries from 2000 until September 2019. Selection criteria: We included randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs of 'working in partnership' interventions meeting these three criteria: both consumer and provider participants meet; they meet jointly and regularly in formal group formats; and they make actual decisions that relate to the person-centredness of health service(s). Data collection and analysis: Two review authors independently screened most titles and abstracts. One review author screened a subset of titles and abstracts (i.e. those identified through clinical trials registries searches, those classified by the Cochrane RCT Classifier as unlikely to be an RCT, and those identified through other sources). Two review authors independently screened all full texts of potentially eligible articles for inclusion. In case of disagreement, they consulted a third review author to reach consensus. One review author extracted data and assessed risk of bias for all included studies and a second review author independently cross-checked all data and assessments. Any discrepancies were resolved by discussion, or by consulting a third review author to reach consensus. Meta-analysis was not possible due to the small number of included trials and their heterogeneity; we synthesised results descriptively by comparison and outcome. We reported the following outcomes in GRADE 'Summary of findings' tables: health service alterations; the degree to which changed service reflects health service user priorities; health service users' ratings of health service performance; health service users' health service utilisation patterns; resources associated with the decision-making process; resources associated with implementing decisions; and adverse events. Main results: We included five trials (one RCT and four cluster-RCTs), with 16,257 health service users and more than 469 health service providers as trial participants. For two trials, the aims of the partnerships were to directly improve the person-centredness of health services (via health service planning, and discharge co-ordination). In the remaining trials, the aims were indirect (training first-year medical doctors on patient safety) or broader in focus (which could include person-centredness of health services that targeted the public/community, households or health service delivery to improve maternal and neonatal mortality). Three trials were conducted in high income-countries, one was in a middle-income country and one was in a low-income country. Two studies evaluated working in partnership interventions, compared to usual practice without partnership (Comparison 1); and three studies evaluated working in partnership as part of a multi-component intervention, compared to the same intervention without partnership (Comparison 2). No studies evaluated one form of working in partnership compared to another (Comparison 3). The effects of consumers and health providers working in partnership compared to usual practice without partnership are uncertain: only one of the two studies that assessed this comparison measured health service alteration outcomes, and data were not usable, as only intervention group data were reported. Additionally, none of the included studies evaluating this comparison measured the other primary or secondary outcomes we sought for the 'Summary of findings' table. We are also unsure about the effects of consumers and health providers working in partnership as part of a multi-component intervention compared to the same intervention without partnership. Very low-certainty evidence indicated there may be little or no difference on health service alterations or health service user health service performance ratings (two studies); or on health service user health service utilisation patterns and adverse events (one study each). No studies evaluating this comparison reported the degree to which health service alterations reflect health service user priorities, or resource use. Overall, our confidence in the findings about the effects of working in partnership interventions was very low due to indirectness, imprecision and publication bias, and serious concerns about risk of selection bias; performance bias, detection bias and reporting bias in most studies. Authors' conclusions: The effects of consumers and providers working in partnership as an intervention, or as part of a multi-component intervention, are uncertain, due to a lack of high-quality evidence and/or due to a lack of studies. Further well-designed RCTs with a clear focus on assessing outcomes directly related to partnerships for patient-centred health services are needed in this area, which may also benefit from mixed-methods and qualitative research to build the evidence base.
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Patients are central to healthcare delivery, yet all too often their perspectives and input have not been considered by providers.1 ,2 This is beginning to change rapidly and is having a major impact across a range of dimensions. Patients are becoming more engaged in their care and patient-centred healthcare has emerged as a major domain of quality.3–6 At the same time, social media in particular and the internet more broadly are widely recognised as having produced huge effects across societies. For example, few would have predicted the Arab Spring, yet it was clearly enabled by media such as Facebook and Twitter. Now these technologies are beginning to pervade the healthcare space, just as they have so many others. But what will their effects be? These three domains—patient-centred healthcare, social media and the internet—are beginning to come together, with powerful and unpredictable consequences. We believe that they have the potential to create a major shift in how patients and healthcare organisations connect, in effect, the ‘perfect storm’, a phrase that has been used to describe a situation in which a rare combination of circumstances result in an event of unusual magnitude creating the potential for non-linear change.7 Historically, patients have paid relatively little attention to quality, safety and the experiences large groups of other patients have had, and have made choices about where to get healthcare based largely on factors like reputation, the recommendations of a friend or proximity.8 Part of the reason for this was that information about quality or the opinions of others about their care was hard to access before the internet. Today, patients appear to be becoming more engaged with their care in general, and one of the many results is that they are increasingly using the internet to share and rate …
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