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OCR for page 47
2
Clinical Research, Patient Care,
and Learning That Is
Real-Time and Continuous
INTRODUCTION
The United States is home to vital and dynamic biomedical research
enterprises. Science-driven care, however, requires a focus beyond advancing
understanding of disease mechanisms. The same level of passion, creativity,
and rigor must be applied to the translation of these discoveries into effec-
tive patient care and improved health outcomes. Several recent reports call
for improvements in the level, quality, and effectiveness of clinical research
through a sharper focus on generating timely information that is relevant
to care decisions faced by patients and providers and on the science of care
delivery (Conway and Clancy, 2009; Dougherty and Conway, 2008; IOM,
2010, 2011).
Current clinical research capacity is underdeveloped, substantially frag-
mented, and limited in its ability to support such work, particularly learning
in real-world settings (Califf, 2009; IOM, 2010, 2011). A more dynamic
clinical research infrastructure that draws research closer to practice is
needed to facilitate ongoing study and monitoring of the relative effective-
ness of clinical interventions and care processes. Innovative research ap-
proaches (e.g., novel study designs, analytical tools, use of course-of-care
data from electronic medical and personal health records) will also acceler-
ate learning (IOM, 2011; Lauer and Collins, 2010).
The papers that follow explore leading opportunities to improve the
efficiency, effectiveness, and volume of clinical research. They also describe
strategies for fostering the development of the capacity and culture needed
for real-time and continuous learning that anticipates research needs and
47
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48 PATIENTS CHARTING THE COURSE
produces evidence that is timely, relevant, and applicable to real-world
care. Patrick Conway, formerly of the Office of the Secretary of the Depart-
ment of Health and Human Services (HHS), reviews the unique nature of
comparative effectiveness research (CER) and its core aim of helping to
inform decisions of patients, clinicians, and policy makers. Recent federal
investments have expanded national capacity for CER, and ensuring the
long-term success of this emerging enterprise will require a near-term focus
on devising a sustainable funding strategy, developing a research agenda for
a balanced portfolio of high-impact topics, selecting methods appropriate to
information needs, and evaluating and reporting progress to the public. Ele-
ments essential to ensuring the availability and use of comparative informa-
tion at the point of decision making are discussed as well. John Noseworthy
and Sherine Gabriel of Mayo Clinic offer insights into what might be pos-
sible if health systems were better engaged in the research enterprise. To
illustrate the potential, they review several examples of the use of clinical
data captured as part of healthcare delivery to improve care quality and
health outcomes. They describe key characteristics of knowledge-driven
healthcare delivery systems of the future, including patient-centered care;
real-time data and feedback; a culture of collaboration, innovation, and
translation; health information technology (HIT); and delivery of high-
value health care.
Without the willing participation of the public and patients as contribu-
tors to learning, however, capacity for research will remain limited. Diane
Simmons and Kenneth Getz of the Center for Information and Study on
Clinical Research Participation review current public and patient attitudes
toward participation in clinical research and offer some suggestions for fos-
tering a culture that better supports and encourages public appreciation of
and participation in such research. Educational and outreach efforts by the
clinical research community and other stakeholders are needed to enhance
public awareness, enable participation, and sustain interest over time.
COMPARATIVE EFFECTIVENESS RESEARCH:
PATIENT, CLINICIAN, AND POLICY NEEDS
Patrick Conway, M.D., M.Sc.
Office of the Secretary, Department of Health
and Human Services (formerly)
Cincinnati Children’s Hospital
National Investments in a Comparative Effectiveness Research Enterprise
The American Recovery and Reinvestment Act (ARRA) of 2009 dedi-
cated $1.1 billion to CER and established the Federal Coordinating Council
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49
CLINICAL RESEARCH, PATIENT CARE, AND LEARNING
(FCC) for CER. The FCC established a common federal government defini-
tion for CER, prioritization criteria for scientifically meritorious research
(Box 2-1), and a strategic framework to guide investment decision making
and priorities, and offered recommendations for initial priorities (Figure 2-1).
The FCC definition of CER is as follows:
Comparative effectiveness research is the conduct and synthesis of research
comparing the benefits and harms of different interventions and strategies
to prevent, diagnose, treat and monitor health conditions in “real world”
settings. The purpose of this research is to improve health outcomes
by developing and disseminating evidence-based information to patients,
clinicians, and other decision makers, responding to their expressed needs,
about which interventions are most effective for which patients under
specific circumstances. (FCC, 2009)
ARRA allocated $400 million to the National Institutes of Health (NIH),
$300 million to the Agency for Healthcare Research and Quality (AHRQ),
and $400 million to the Office of the Secretary for CER. The Office of
the Secretary funding supported an array of data infrastructure projects,
whose focus ranged from claims data to clinical data networks to patient
registries. These investments also focused on selected priority populations,
such as children and persons with multiple chronic conditions (Conway
and Clancy, 2009). Another major priority for the Office of the Secretary
BOX 2-1
Federal Coordinating Council for
Comparative Effectiveness Research
• rioritization criteria for scientifically meritorious research
P
• otential impact (based on prevalence of condition, burden of disease, vari-
P
ability in outcomes, costs, potential for increased patient benefit or decreased
harm)
• otential to evaluate comparative effectiveness in diverse populations and
P
patient sub-groups and engage communities in research
• ncertainty within the clinical and public health communities regarding man-
U
agement decisions and variability in practice
• ddresses need or gap unlikely to be addressed through other organizations
A
• otential for multiplicative effect (e.g., lays foundation for future CER such as
P
data infrastructure and methods development and training, or generates ad-
ditional investment outside government)
SOURCE: FCC, 2009.
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50 PATIENTS CHARTING THE COURSE
Human and Dissemination and
Research Data Infrastructure
Scientific Capital Translation
Priority Populations
Cross-
Cutting
Priority Conditions
Priority
Themes
Types of Interventions
Primary investment Secondary investments Supporting investments
FIGURE 2-1 Federal Coordinating Council (FCC) strategic framework and rec-
ommended Office of the Secretary investment priorities for CER. This framework,
including core activities (research, human2-1.eps
Figure and scientific capital, data infrastructure,
and dissemination and translation) and cross-cutting priority themes (populations,
conditions, and intervention types), was developed by the FCC to guide investment
decisions and priorities.
SOURCE: FCC, 2009.
investment was dissemination of CER findings and their incorporation into
practice. This effort will encompass both clinicians and patients, and will
utilize networks and the delivery system. Finally, the Office of the Secretary
investments targeted selected research topics—such as delivery systems; pre-
vention; behavioral change; and priority populations, including racial and
ethnic minorities and persons with disabilities—to complement the funding
from AHRQ and NIH. Finally, the ARRA CER investment included fund-
ing for an ongoing inventory of CER and evaluation of the CER portfolio.
The Affordable Care Act (ACA) of 2010 included additional focus and
funding for CER. Specifically, it established the Patient-Centered Outcomes
Research Institute (PCORI). The duties of PCORI include identifying re-
search priorities and establishing a research agenda. The Institute will have
a 17-member Board of Governors and several expert advisory panels. Its
budget will increase over time and likely exceed $600 million annually.
For the national CER program to have maximum impact on health
and the value of healthcare delivery, the following five next steps have been
proposed (VanLare et al., 2010):
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CLINICAL RESEARCH, PATIENT CARE, AND LEARNING
1. Develop an overall funding strategy, influenced by clinicians and
patients and the program’s stakeholder advisory board.
2. Establish an initial list of priority topics, and evaluate the current
state of knowledge about each.
3. With input from the advisory board and decision makers, select
the research methods appropriate to fill the gaps in knowledge on
a particular topic/question.
4. Strive for a balanced portfolio of high-impact research topics.
5 Evaluate progress, and report to the public.
CER Enterprise Implementation
Multiple additional considerations are involved in implementing a suc-
cessful CER enterprise. First, the research methods must address the level
of evidence necessary to influence decision makers. The level of evidence
will vary based on the question and decision involved, but certain decisions
may not require randomized controlled trials. Decision makers, includ-
ing patients and clinicians, should be actively engaged in the planning
and funding of research so CER meets their needs. The level of evidence
needed to influence decisions should be considered an integral part of
funding decisions and research designs. In addition, funding is needed to
develop research methods and build understanding of how the methods
used and the communication of findings will best meet decision makers’
needs (Chalkidou et al., 2009).
The FCC (2009) and IOM (2009) reports on CER were strongly in-
fluenced by public input, and ARRA includes funding for actively seeking
input to guide CER (e.g., horizon scanning). Building on this work to
involve stakeholders, PCORI should focus its efforts on maintaining and
increasing clinician, patient, and other stakeholder input. This input is im-
portant because one of the unique aspects of CER is that it must be guided
by the needs of routine practice and consumers, which involves a different
paradigm from that which informs traditional, investigator-driven research.
To garner input efficiently and effectively, technology and other means of
obtaining “real-time” input from a broad sample of patients, clinicians, and
other stakeholders are needed. Finally, a feedback loop from users and im-
plementers of research back to the research enterprise is essential. Examples
of such feedback loops exist in certain delivery systems and networks, but
they need to become the rule as opposed to the exception.
The FCC report and subsequent ARRA funding (especially that for the
Office of the Secretary) focused on dissemination and adoption. Without
any investment in adoption, the CER enterprise will fail to translate com-
parative evidence into improved health outcomes (Dougherty and Conway,
2008). To better understand the factors underlying successful adoption
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52 PATIENTS CHARTING THE COURSE
interventions will require research, supported by HIT as a tool for both
driving and measuring adoption. Although challenging, successful adoption
will provide significant rewards by allowing the healthcare system to deliver
higher-quality care, better value, and better population health, fundamen-
tally transforming U.S. health care.
Although research funders often do not systematically evaluate the
impact of their research investments. Evaluation is critical not only for
measuring impact but also for understanding how to improve future re-
search investments. In contrast, the Office of the Secretary CER invest-
ment included evaluation of ARRA CER funding to focus on impact and
guide future CER investments. Going forward, the CER research enterprise
should be accountable to the public by evaluating investments and publicly
reporting the evaluation results.
Concluding Observations
Overall, CER represents an opportunity to focus research on the needs
of clinicians, patients, policy makers, and other decision makers. Unfortu-
nately, all of these groups often are faced with health-related decisions for
which insufficient evidence exists to guide decisions or the evidence is not
adequately available at the point of decision making. Therefore, the evi-
dence must be generated to meet decision makers’ needs and disseminated
effectively to the point of decision making, in order to inform care and drive
better outcomes and value.
HEALTH SYSTEMS AS RESEARCH PLATFORMS:
ENHANCING SCIENCE, VALUE, AND INNOVATION
John Noseworthy, M.D., and Sherine Gabriel, M.D., M.Sc.
Mayo Clinic
The IOM’s Learning Health System series of workshops has defined
foundational elements for a healthcare system that enables both the imple-
mentation of best care practices and the real-time generation and applica-
tion of new evidence. This paper focuses on one of these elements—health
systems as research platforms. It considers how healthcare organizations
can be structured to support a system that advances clinical research and
produces and applies evidence that is timely, relevant, and applicable to
real-world care. One example of such a system is Mayo Clinic, a health
system with a long tradition of creating and sustaining research platforms
built upon its rich clinical practice.
Traditionally, leading healthcare organizations have fostered the incor-
poration of discovery and clinical research into clinical practice. For more
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CLINICAL RESEARCH, PATIENT CARE, AND LEARNING
than a hundred years, Mayo Clinic has applied a singular focus on excellent
patient care through its primary value—“The needs of the patient come
first”—and its mission statement—“Mayo Clinic will provide the best care
to every patient every day through integrated clinical practice, education,
and research.” Figure 2-2 shows a page from a patient ledger that contains
the oldest medical records at Mayo Clinic. Written by Dr. William Worrall
Mayo in 1866, it indicates that the patient record is “left open for further
thought and research,” exemplifying the philosophy of continuous learning
during the course of clinical care.
Mayo Clinic has applied its culture of patient-centeredness to incorpo-
rate advances from clinical research into practice as expeditiously as pos-
sible. Research has always been a fundamental component of Mayo’s core
activities. The “conventional” approach of identifying key basic science and
clinical research questions, publishing the results of these hypothesis-driven
studies, and incorporating them into practice has helped Mayo Clinic grow
its reputation as a knowledge-driven, patient-centered healthcare system.
Three examples of this conventional approach are the Rochester Epidemiol-
“Left open for further thought
and research”
William Worrall Mayo, MD
MAYO CLINIC | ©2010 MFMER 1
FIGURE 2-2 Mayo Clinic patient ledger, 1866.
Figure 2-2.eps
SOURCE: Reprinted courtesy of the Mayo Clinic.
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54 PATIENTS CHARTING THE COURSE
ogy Project, the Total Joint Registry, and the recently completed Warfarin
Project. A description of each of these efforts is followed by a discussion of
two new transformational initiatives currently under way, designed to meet
the healthcare needs of the future.
Rochester Epidemiology Project
The Rochester Epidemiology Project (REP) is a long-standing collabo-
ration among healthcare providers in Olmsted County, Minnesota (Kurland
and Molgaard, 1981; Kurland et al., 1970; Melton, 1996, 1997). Many
decades ago, these providers formally agreed to share medical records col-
lected during the course of care of Olmsted county residents in order to
study the health and illnesses of people in this community. Inferences drawn
from this unique population-based resource could then be used to inform
and improve health and health care in the entire country. The REP is one of
a few venues where population-based research can be conducted passively
and on a routine basis. REP studies typically address disease incidence
and prevalence, time trends, risk and protective factors, effectiveness of
treatments, natural history and outcomes, genetic factors, quality of care,
and cost of care through careful identification of cases and controls and
of exposed and nonexposed individuals. The infrastructure for the REP
has been NIH-funded since 1966, supports many individual NIH-funded
research grants (approximately 40 during the past 5 years), and has yielded
approximately 2,042 peer-reviewed research papers to date. From these
publications have come such observations as the following: the occurrence
of Guillain-Barré Syndrome is increased only slightly by swine flu vaccina-
tion (Beghi et al., 1985); silicone breast implantation carries a high risk of
surgical complications, but is not associated with previously claimed signifi-
cant autoimmune adverse sequellae (Beghi et al., 1985; Gabriel et al., 1994,
1997); routine immunizations do not increase the risk of autism (Barbaresi
et al., 2005); and prophylactic bilateral oophorectomy is associated with
both increased mortality and an increased risk of neurological disorders
(Rocca et al., 2006, 2007, 2008).
Total Joint Registry
The Mayo Clinic Total Joint Registry1 is the most comprehensive joint
replacement registry in the world. The database was established in 1969,
has been carefully maintained since that time, and now contains data on
97,500 arthroplasties. Structured standardized information is gathered from
1 See http://www.regulations.gov/search/Regs/home.html#documentDetail?R=090000648098
c1d0 (accessed October 11, 2010).
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CLINICAL RESEARCH, PATIENT CARE, AND LEARNING
patients before, during, and at scheduled intervals after their surgeries for the
lifetime of the patient and the orthopedic implant. This registry has allowed
for comparison of surgical techniques, implant types, patient demographics,
comorbid conditions, and long-term outcomes. It has allowed physicians to
determine which surgical practices and implant models are most effective
over time and has informed decision making on these issues. The registry has
been a valuable clinical and research tool, allowing orthopedic surgeons, for
example, to compare planned hip replacement surgery with 35,000 such op-
erations performed since 1966. Work based on this registry has enabled con-
tinuous improvement in the processes of care, favorably influencing lengths
of stay, resource use, and the results of care (i.e., delivery of high-value care).
The registry has served as a data source for more than 800 academic publica-
tions. It has enabled CER and has led to improvements in information sys-
tems that facilitate and enhance the continuity of care delivery after surgery.
Mayo Clinic Warfarin Project
The Mayo Clinic Warfarin Project is a third example of conventional,
focused clinical research designed to improve the quality of care. This
intervention was launched with the goal of reducing warfarin-related over-
anticoagulation, which is acknowledged to be a leading iatrogenic illness. In
2005, 18,700 inpatients were treated with warfarin at Mayo Clinic. It was
determined that 3.5 percent experienced iatrogenic overanticoagulation,
with a score greater than 5.0 on the blood coagulation International
Normalized Ratio (INR) laboratory test, resulting from in-hospital warfarin
administration, and no definitive, published, evidence-based guidelines for
administering warfarin in the hospital existed. We recognized that there was
considerable variability in risk for iatrogenic overanticoagulation across
the five states where Mayo Clinic practices. Therefore, a prospective study
was designed to develop a standardized warfarin protocol that would
improve outcomes. The goal was to reduce the number of inpatients who
had a single recording of an unsafe inpatient INR (greater than 5.0) from
3.5 percent to less than 1.5 percent. This project involved standardized rule-
based algorithms supported by the prescriber using computerized provider
order entry, with the hospital pharmacist determining the final dose from
these algorithms. This work takes advantage of the principle of reflexivity;
the prescribing system algorithm was improved dozens of times through
the “plan, do, study, act cycle” based on surveillance, performance data,
and user feedback. Since implementation of the standardized, rule-based
algorithms, consistently fewer than 1.5 percent of Mayo Clinic warfarin
inpatients have had an INR above 5.0, and there has been no increase in
the proportion of patients with an INR below 1.7 after the third dose. Thus
not only was the risk of potential hemorrhage reduced, but also the risk
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56 PATIENTS CHARTING THE COURSE
of clotting was not commensurately increased. This change in practice has
significantly reduced the risk of inpatient warfarin-related adverse events.
Transformational Initiatives
The High Value Healthcare Initiative
A learning healthcare system has as its central focus improving the value
of care. For many years, Mayo Clinic has maintained an institution-wide
emphasis on quality (best clinical outcomes, safety, and service), which
has been applied both to the care of individual patients and through
population-based strategies to manage chronic disease across communities of
patients. Recently, Mayo Clinic has gone beyond its focus on the numerator
(quality in terms of best outcomes, safety, and service) of the value equation
(e.g., value = quality/cost) to address the denominator (i.e., the cost of care
over time). Together with the Dartmouth Institute, Intermountain Health-
care, and the Geisinger Health System, Mayo is proposing a pilot project
for the Innovation Center at Centers for Medicare & Medicaid Services
(CMS) called the High Value Healthcare Project. This represents the first
step in a broad-based initiative that will benchmark the costs of best prac-
tices over time, implement evidence-based best practice and patient shared
decision-making models, and study new reimbursement models that better
align payments with the outcomes of patient care. Together with similar
initiatives under way around the country, the High Value Healthcare Initia-
tive is motivating a fundamental transformation of health systems from their
traditional focus on compliance with process to a more meaningful focus on
results, outcomes, and value.
As famously reported by Balas and Boren (Balas and Boren, 2000), the
lag time between the discovery of more efficacious forms of treatment and
their incorporation into practice is unacceptably long—about 15–20 years.
Moreover, a majority of patients at any given time receive care that is not
supported by evidence-based research (Advisory Commission on Consumer
Protection and Quality in the Health Care Industry, 1998). Stakeholders
across the healthcare system—from patients to practitioners to payers—
recognize the need for disruptive change to bring about fundamental im-
provements in health care. It is becoming increasingly apparent that such
change requires new information systems to accelerate discovery, drive
clinical research, identify best practices, and diffuse these practices rapidly
across the profession.
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CLINICAL RESEARCH, PATIENT CARE, AND LEARNING
The Mayo Clinic Enterprise Data Trust
The Mayo Clinic Enterprise Data Trust is an example of a centralized
repository system created to manage, integrate, and share collective infor-
mation resources with appropriate regulatory protections (Figure 2-3). This
consolidated infrastructure can, for example, integrate biospecimen-related
data generated by research core laboratories with phenotypic data extracted
from clinical records through natural language processing techniques, ana-
lyze those data to develop improved biomarkers to guide therapy, and
provide that information to physicians for use in caring for patients. Data
and biospecimens collected during the course of care are fed back into the
system to inform and improve the care of future patients. Systems such as
this are needed to enable the evolution to a knowledge-driven healthcare
delivery system.
Conclusions
The examples discussed above demonstrate how a patient-centered,
knowledge-driven healthcare delivery system can serve as a research plat-
FDA
CLINICAL RESEARCH
Therapeutics
REGULATORY
Physician
Biomarkers
Clinical,
Translational and
Basic Science
Bioinformatics
• Epidemiology
Biostatistics
• Pharmacology
• O ncology
• Pathology
• etc
ANALYTICS
EXPERIMENTAL
Clinical Notes
CORE Labs
Patient Lab Test Gene expression
Results Genotypes
Proteomics
REGULATORY
BAP
Biospecimens
Biospecimens
INSTITUTIONAL
REVIEW BOARD
FIGURE 2-3 Schematic of Mayo Clinic Enterprise Data Trust.
SOURCE: Reprinted courtesy of the Mayo Clinic.
Figure 2-3.eps
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58 PATIENTS CHARTING THE COURSE
form both to improve outcomes for future patients and to identify the
most compelling questions for future research. More important than these
specific examples, however, are the underlying conceptual model and the
set of fundamental principles upon which these (and other) examples are
built. Although the specific examples may not be replicable elsewhere, the
underlying model and key characteristics are widely translatable and trans-
portable around the country and, indeed, around the world.
Figure 2-4 illustrates a model for a knowledge-driven healthcare delivery
system of the future. As shown, knowledge generated from routine clinical
settings is integrated with biological information garnered from biospecimen
banks and other sources; aggregated and analyzed using sophisticated data
warehousing and computational tools; and then used to improve patient
outcomes through enhanced clinical practice, business processes, education,
and research. The system rests on a foundation of data security and gover-
nance, metadata, and terminology standards.
The key characteristics of a knowledge-driven healthcare delivery sys-
tem are summarized in Box 2-2. Patient-centeredness must be at the core of
Integrated Objectives Outcomes
Patient Data Synthesis
Database
Data Genetic
epidemiology
( Controls and Research Etiology
disease states)
Progression
Patient
Decision Support
Clinical Risk analysis/
Data prevention
• L ab
Diagnosis
• Imaging Cure
Enterprise Clinical Prognosis
• EMR Analytics/ Wellness
Data
• Dept. Treatment
Computation
Trust Quality
systems Stratification
(EDT) of life
& Rx planning
Biological Value
(Biobanking) Public
Educational
Profession
Clinical practice
Research grants
Business
DLMP, M ML,
MVSS
Licensing
Security
Data Governance
Meta Data, Standards
and Ontologies (informatics)
FIGURE 2-4 Model for a knowledge-driven healthcare delivery system. The model
focuses on generating and synthesizing knowledge in daily clinical settings to advance
research, education, clinical practice, and business operations to improve patient
Figure 2-4.eps
outcomes.
SOURCE: Reprinted courtesy of the Mayo Clinic.
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CLINICAL RESEARCH, PATIENT CARE, AND LEARNING
BOX 2-2
Characteristics of the Knowledge-Driven
Healthcare Delivery System of the Future
• atient-centered care—a focus on quality (best results) and coordination of care
P
• eal-time data and feedback for providers at the point of care (horizon scanning)
R
• culture of collaboration, innovation, and translation of scientific knowledge
A
into improved health for patients and communities
• ealth information technology systems—integration, standardization, interoperability
H
• elivery of high-value health care in an information-enabled single practice
D
health care. Although patient-centered care is often assumed, it is but by no
means universally applied. Providers must design and implement systems to
be focused on quality and team-based, integrated, coordinated care centered
on the patient. To enable the evolution to a knowledge-driven, learning
healthcare delivery system, future HIT systems must have the capability
to provide real-time data and real-time feedback to providers at the point
of care/point of need. This capability will require scanning disparate in-
ternal and external data resources to rapidly find answers to scientific,
clinical, and operational questions. HIT systems must also be integrated,
standardized, and highly interoperable. Finally, the delivery of high-value
care in the information-enabled practice of medicine requires a culture of
collaboration, innovation, and translation of scientific knowledge into im-
proved health for patients and communities. Although perfect and complete
actualization of the conceptual model for each of the above characteristics
may be a long way off, an intense focus on the development of integrated,
patient-centered, and knowledge-driven healthcare delivery systems will
lead to better health care and better health.
ENHANCING THE CULTURE OF PATIENT
CONTRIBUTIONS TO LEARNING IN HEALTH CARE
Diane Simmons and Kenneth Getz, M.B.A.
Center for Information and Study on Clinical Research Participation
How can a durable relationship be built with the millions of past, pres-
ent, and potential future clinical research study volunteers? A portfolio of
strategic initiatives is needed to regain public trust in the clinical research
enterprise and establish a culture that welcomes input from patients. Since
its founding in 2004, the nonprofit Center for Information and Study on
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60 PATIENTS CHARTING THE COURSE
Clinical Research Participation has developed an effective, multifaceted
strategy of outreach and education to improve public understanding of the
clinical research process and the important role of participation in advanc-
ing medical science. After a discussion of the current culture, this paper
presents a number of examples of strategic initiatives for recruiting, retain-
ing, and sustaining a community of study participants who will ultimately
become the ambassadors for learning in health care.
Current Culture
During the past decade, public confidence and trust in the clinical
research enterprise has eroded steadily (Center for Information and Study
on Clinical Research Participation, 2006; HarrisInteractive, 2007; Kaiser
Family Foundation, 2008). Distrust of clinical research professionals and
of those organizations responsible for ensuring patient safety has increased
dramatically. Public polls reveal startling statistics. For example, a 2007
poll among 1,726 U.S. adults found that 27 percent of respondents dis-
trusted the Food and Drug Administration (FDA) “somewhat” or “very
strongly.” That same poll found that only 31 percent of respondents be-
lieved that the FDA is effective at ensuring safety, down from 56 percent
who held this belief in 2004 (HarrisInteractive, 2007). Equally alarming,
nearly half (46 percent) of the 1,726 Americans polled said they distrusted
Capitol Hill officials who govern regulatory oversight and drug develop-
ment processes (HarrisInteractive, 2007).
Four of ten respondents (42 percent) distrusted pharmaceutical and
biotechnology companies. The poll showed that a significantly higher per-
centage (39 percent) gave poor ratings to pharmaceutical and biotechnology
companies for failing to serve consumers as compared with 1997, when
19 percent of Americans surveyed rated pharmaceutical and biotechnology
companies on this item poorly (HarrisInteractive, 2007).
Nearly half (44 percent) of the 1,695 American adults polled in a Janu-
ary 2008 survey likewise reported having an unfavorable view of pharma-
ceutical and biotechnology companies. In that same survey, 27 percent of
Americans said they did not trust these companies to offer reliable informa-
tion about drug side effects and safety. And 45 percent said they did not
trust research sponsors to inform the public quickly when safety concerns
with a drug are uncovered (Kaiser Family Foundation, 2008).
The public displays similar levels of distrust in principal investigators
and their study staff. A self-administered survey conducted among 717
U.S. adults in 2007 found high levels of public distrust in clinical research
staff. This level of distrust was significantly higher among minority adults
(HarrisInteractive, 2004). Nearly half (49 percent) of white respondents
and 73 percent of minority respondents reported that it was “very likely”
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CLINICAL RESEARCH, PATIENT CARE, AND LEARNING
or “somewhat likely” that they might be used as guinea pigs without their
consent. One of four (25 percent) minority respondents and 22 percent of
white respondents believed that their doctors would expose them to un-
necessary risk in clinical trials (Braunstein et al., 2008).
The majority of respondents (72 percent) in a 2002 poll said they be-
lieved that physicians get involved in clinical research to help patients find
new and better treatments (HarrisInteractive, 2002). Still, one of four said
they believed that doctors and study staff are motivated to recruit volun-
teers primarily by money and selfish interests. In a 2005 survey, 25 percent
of respondents said they believed physicians participate in clinical research
to receive money from pharmaceutical and biotechnology companies, and
another 20 percent said that physicians participate primarily for fame,
glory, and publication rights (HarrisInteractive, 2005).
By extension, public distrust in clinical research professionals has
tainted the public’s view of clinical research volunteers. In a 2002 poll, 8 of
10 Americans said they believed that study volunteers are taking a gamble
with their health (HarrisInteractive, 2002). A 2006 survey conducted among
900 U.S. adults found that one of four believed people choose to participate
in clinical research because they are “very sick without any other options”
or they are “looking to make money.” A smaller percentage—19 percent—
believed that people choose to participate in clinical trials to benefit the
public’s health. In that same survey, 34 percent of respondents said they “do
not admire” people who volunteer for clinical trials (Center for Information
and Study on Clinical Research Participation, 2006).
As public appreciation for study volunteers has waned, public willing-
ness to participate in clinical trials has also dropped. Research!America,
for example, reported that in 2004, 55 percent of those polled said they
would be willing to participate in a clinical trial, down from 63 percent in
2001 (Woolley and Propst, 2005). A later public poll, conducted in 2007,
found that only 41 percent of white adults and 28 percent of minority
adults would be “very likely” or “likely” to participate in clinical trials
(Braunstein et al., 2008).
Investigative sites report that growing levels of public distrust have
contributed to delays in bringing new treatments to market and to increased
drug development costs. Since 2000, spending on patient recruitment pro-
motional programs by investigative sites and research sponsors has grown
by 12 to 14 percent annually, reaching more than $500 million in 2003
(Korieth, 2004). Enrollment rates dropped from 75 percent in 2000 to
59 percent in 2006, and retention rates fell from 69 percent to 48 percent
during that same period (Kaitin, 2008).
In an attempt to understand how to improve patient recruitment and
retention rates, the Center for Information and Study on Clinical Research
Participation conducted focus groups among study volunteers to probe for
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62 PATIENTS CHARTING THE COURSE
factors that most inform and educate clinical research participants. This
research was conducted in 2009 at Piedmont Medical Group in North
Carolina. In these focus groups, participants emphasized the essential role
of study staff and healthcare professionals in volunteer recruitment and re-
tention. They consistently described relationships with study staff as tough
but fair, disciplined but supportive. At a time when recruitment and reten-
tion strategies and tactics tend to marginalize the role of study staff and
trusted healthcare professionals, the results of these focus groups strongly
suggest the need to engage these professionals more effectively as real assets
in the clinical trial process.
The focus group participants revealed core motivations of all study
volunteers regardless of age and socioeconomic status. These motivations
can serve as a blueprint for patient and public education and outreach.
Study volunteers
• want to feel that they are taking control of their medical condition
and well-being,
• want to develop personal relationships with study staff,
• want to be treated as human beings, and
• want to know that their participation will make a difference.
Participating in medical research as a way to steer personal and public
health reinforces the drive toward patient-centered health care. Yet the
focus groups clarified that “patient-centered” does not mean that they want
medical autonomy. Despite common expressions such as “take control,”
study participants from the focus groups explained that they do not seek
total independence in their efforts to improve their well-being. The prospect
of being accountable to the research coordinator spurred and sustained
volunteers’ interest in trials. In fact, the volunteer–study staff relationship
forms and solidifies at several critical junctures. When research sites reach
out to potential volunteers with the right messages and modes of commu-
nication at decisive moments and invite them to begin conversations, the
relationship grows into a lasting commitment to the center and its staff.
The focus group participants’ comments show that money-focused
recruitment campaigns and comparisons of research volunteers to “guinea
pigs” or “lab rats” depersonalize the trial experience and keep the volun-
teers from feeling as though they are truly part of an extended research
team. Typical perceptions of clinical research participation must shift before
people can take part proudly and comfortably in a research community.
The emphasis on monetary compensation in media and recruitment rheto-
ric impedes public and participant recognition that volunteers are part of
a vital exchange in which they are compensated for sacrificing their time,
effort, and even physical welfare.
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CLINICAL RESEARCH, PATIENT CARE, AND LEARNING
To be effective, the education provided before and after trials must reflect
what volunteers expect, need, and want to know about clinical research. The
public’s primary source for education about the clinical research enterprise
is the media, which tend to focus on sensationalistic accounts of human
error, concealment, fraud, and corruption. More than two-thirds (69 per-
cent) of Americans are exposed to information on clinical research studies
through television, radio, print media, and Internet advertising. Only one
of seven adult Americans is exposed to information about clinical research
studies from a primary or specialty care physician (HarrisInteractive, 2004).
Although the public has the greatest trust in information from healthcare
providers, the medical and health professional communities are largely absent
from efforts to educate the public and prospective volunteer communities. In
a recent survey conducted among board-certified physicians in active commu-
nity practices throughout the United States, fewer than half reported referring
their patients to clinical trials, with an average referral rate for each physician
of less than one patient per year (Getz and Faden, 2008).
Without broad understanding and context, recruitment advertising
and promotional messages are met with, at best, passing curiosity from
the public and prospective volunteers. Only 20 percent of those diagnosed
with severe and life-threatening illnesses report considering clinical trials
as a healthcare option (HarrisInteractive, 2004). Despite a wealth of on-
line information available, less than 5 percent of the general public knows
where to find information about relevant clinical trials (Getz, 2004). And
the public is largely unaware of where clinical research is taking place. A
2005 public poll found that 62 percent of respondents were unable to name
a single institution, company, or organization where medical and health re-
search is conducted (Woolley and Propst, 2005). Research sponsors rarely,
if ever, respond to media coverage, as government and corporate employees
are usually instructed not to interact with journalists for fear of bringing
more attention to a story or of appearing defensive and self-serving. As a
result, the public is receiving a largely one-sided education in the clinical
trials industry from the media.
Outreach Initiatives and Their Impact
If the public is to be engaged, the stage must be set with a national
public education media campaign. The Center for Information and Study
on Clinical Research Participation developed a public service campaign,
with pro bono support from the international advertising agency Ogilvy
HealthWorld, to educate and win over the public regarding the importance
of participation in clinical research. During the campaign’s yearlong de-
velopment process and extensive focus group testing, strong support was
expressed for the easy-to-remember messaging and acknowledgment of or-
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64 PATIENTS CHARTING THE COURSE
dinary people’s contributions to public health. During screenings before test
audiences, the ads were lauded for their “humanity and emotional appeal.”
Viewers declared, “These people are heroes in their own way,” “They’ve
done something great for all of us,” and “I see the benefit of clinical research
to society.”
This “Medical Heroes” public service campaign was market tested in
30 sites across 18 U.S. markets by Eli Lilly and Company. In the first wave
of the market test, the control group was established as 12 markets that ran
their typical recruitment ads; in 6 comparable markets, concurrent “Medi-
cal Heroes” ads were run, as well as recruitment ads, and these markets
showed a 38 percent increase in patient recruitment rates relative to the
control group. The test was repeated, and the results of the second wave
showed that rates of response to recruitment ads more than doubled in the
markets where the “Medical Heroes” campaign was run. The campaign
met its ultimate goal of providing the public with increased awareness
of research participation and an improved perception of clinical research
volunteers.
Another Center for Information and Study on Clinical Research Par-
ticipation initiative is a grassroots education and outreach process known
as “AWARE for All-Clinical Research Education.” AWARE programs, held
in major cities across the United States, bring together disease advocacy
groups, hospitals and healthcare organizations, educational institutions,
and community organizations to provide AWARE’s message directly to
their constituents. In addition, distinguished local politicians and opinion
leaders, physicians, healthcare providers, and clinical research professionals
serve as keynote speakers and workshop leaders—all volunteering their
time to help educate the public.
To date, more than 300,000 people have been impacted by the pro-
gram. AWARE has put a human face on the people who volunteer for
clinical trials while building public understanding of the risks and benefits
of participating. The initiative is creating a movement at the local level,
and there is a need to bring this form of outreach to many more communi-
ties. When asked whether they were more or less likely to participate in
a clinical trial after attending AWARE, 75 percent of attendees responded
“more likely.”
An additional example of an outreach initiative is post-trial commu-
nication with research volunteers. The Center for Information and Study
on Clinical Research Participation and Pfizer collaborated to test a new
process for routinely communicating clinical trial results to study volunteers
after their participation has ended. Between June and December 2009, trial
results for Celebrex®/Celecoxib and Sutent®/Sunitinib were translated into
lay language by a team of consumer, science, and medical writers and pub-
lished in print, web, and audio formats. These summaries were then tested
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CLINICAL RESEARCH, PATIENT CARE, AND LEARNING
in focus groups among volunteers who had participated in the studies. The
pilot study results demonstrate that a process for preparing and disseminat-
ing summaries of trial results to patients following their participation in
clinical trials is feasible. Moreover, patients reacted very positively to the
variety of formats and showed marked improvement in their comprehen-
sion of their clinical trial findings. Study personnel are also very receptive
to disseminating summaries of trial results to their volunteers.
A final example of a public education and outreach initiative is the devel-
opment of a traveling exhibit for science museums. Still in the preliminary
planning stages, such an exhibit would provide inquiry-based, multimedia
learning experiences focused on the how-to and importance of health re-
search as presented by practicing scientists. It would use an innovative mix of
video storytelling and digital support technologies to show people how real-
world scientists conduct their research and create a continuum from basic to
translational science to clinical trials that produce new treatments and solu-
tions. This type of exhibit would highlight what it means to participate in a
clinical trial and the impact of participation on science and drug discovery.
Conclusions
Despite low levels of trust and confidence today, there is no evidence
to suggest that the public will abandon the clinical research enterprise out-
right. A foundation of general public support exists on which to rebuild
public confidence and trust through education and outreach initiatives.
Such initiatives need to focus on improving public awareness and apprecia-
tion of the study volunteer and the value of clinical research to the public
health; repairing the credibility of research sponsors, study staff, and regu-
latory and human subject protection professionals; and engaging the public
as partners in the development of new medical and health advances. Given
how far public support has fallen, however, there is no time to waste in
repairing and rebuilding trust and confidence.
To enhance the culture of patient contributions to learning in health
care, a portfolio of strategic initiatives is needed, as shown in Figure 2-5.
If general education about and awareness of the clinical research process
are enhanced and if patients are enabled to participate because of the sup-
port network and tools provided to help them become active participants
in clinical trials, recruitment and retention in trials will improve. With this
solid foundation, volunteers will become a community of participants and
ultimately the ambassadors of a process that advances medical science
and improves the public health.
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66 PATIENTS CHARTING THE COURSE
SUSTAIN
Community
of
Participants
and
Ambassadors
RECRUIT AND
RETAIN
ENHANCE ENABLE
General Support
Education and Network and
Awareness Tools
FIGURE 2-5 Model for enhancing the culture of patient contributions to learning
Figure 2-5.eps
in health care. A portfolio of strategic initiatives is needed that enhances the public’s
general education about and awareness of the clinical research process and enables
patients to become active participants in clinical trials. This foundation will lead to
improvements in patient recruitment and retention and ultimately to the formation
of a community of research volunteers.
SOURCE: Center for Information and Study on Clinical Research Participation
model—permission for use in this publication authorized by Diane Simmons, Presi-
dent and CEO.
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