PROCEEDINGS
OF THE 30TH BETHESDA CONFERENCE. THE FUTURE OF ACADEMIC
CARDIOLOGY. BETHESDA, MARYLAND, OCTOBER 26-27, 1998.
JACC Vol. 33, No. 5, April 1999:1091-1135
30th
Bethesda Conference:
The Future of Academic Cardiology*
Task
Force 2: Research
Jeffrey
S. Borer, MD, FACC, Co-Chair, Robert A. Vogel,
MD, FACC, Co-Chair
EFFECT
OF CURRENT NATIONAL MEDICAL PRIORITIES AND REIMBURSEMENT
STRATEGIES ON CARDIOVASCULAR RESEARCH ACTIVITIES IN
ACADEMIC MEDICAL CENTERS
Scope
of the Problem
The
value of academic cardiological research. During
the past 40 years, management of patients with cardiovascular
diseases has changed dramatically, and primary prevention
of disease has emerged as a practical reality. Extraordinary
benefits in length and quality of human life have resulted.
The primary reason for these developments has been the
body of new knowledge created by a sustained research
effort marked by both its quantity and its quality.
The research has resulted from a partnership between
academic (medical school-affiliated teaching centers)
and nonacademic medical centers, industry and government
in which the academic centers traditionally have played
a leading role.
Current
national medical priorities and reimbursement strategies
threaten the potential for similar efforts by academic
centers in the future and, thus, threaten the productive
relation between medical centers, industry and government.
Specifically, the ongoing reorganization of delivery
and funding of medical services and funding of research
jeopardizes the development and even the existence of
the clinician-investigator, the clinically trained and
clinically active physician who is centrally involved
in shaping research goals and effecting research projects.
In the past, development of the clinician-investigator
has been a primary contribution of the academic medical
center. Resolution of this issue, with survival of the
clinician-investigator, is critical to continuing reduction
of the burden of cardiovascular diseases in our society.
To understand the value of the academic medical center
in cardiovascular research it is necessary to define
research, the processes it entails and the research
products of academic centers in the recent past.
Within
the scientific community, research is a formal discipline
for creation of new knowledge. The process involves
application of the scientific method (hypothesis generation
and formal hypothesis testing according to long-accepted
principles for this purpose) to the solution of problems
and questions, using prespecified methods which are
ethically justifiable. The product of research is the
scientific paper; research is not complete until it
has been reported to the scientific community in sufficient
detail so that it can be replicated, criticized and,
in the case of biomedical research, applied in a process
aimed to benefit society (1).
The
foregoing definition implies a degree of rigor which
generally is employed by those with formal research
training. Many academic cardiologists (i.e., those who
are employed by a medical school and who are responsible
for teaching), particularly those who have earned a
PhD as well as an MD, have undergone such training and
embrace research as defined above. However, as discussed
below, formal training in the principles of research
is not necessarily integrated into the medical school
curriculum, nor is it a part of most cardiology fellowship
training programs. Rather, for most cardiologists, research
training occurs during an apprenticeship under a mentor,
and instruction in the formal principles of the discipline
may be lacking. Thus, many cardiologists, particularly
those without formal research training and those involved
solely in clinical care, may be relatively unfamiliar
with the definition of research as stated above, and
with operational principles which the definition entails.
For
society at large, understanding of the definition and
methods of scientific biomedical research varies according
to individual background. However, even among well educated
persons, the concept of research generally is understood
as information gathering. The concept does not necessarily
encompass the process and, particularly, the rigor required
for proof of conclusions by the trained and experienced
researcher. This difference in the perception of research
partially accounts, for example, for the public (and
professional) outcry when drugs are not approved on
the basis of observational or uncontrolled data. The
public perceives research quantity to be "very
large" in the U.S., a perception fed by National
Institutes of Health budgets of many millions of tax
dollars as quoted in the public press. In general, the
public perceives research quality to be very high, as
well; indeed, though it is seldom the focus of intense
consideration, the current generation believes that
research "will find the answers" and has difficulty
understanding why "they haven't found the answer
to that [problem] yet."
Perceptions
have changed during the past decade, most particularly
because of the proliferation of communications technologies.
These have enabled increasingly detailed and focused
questioning of the scientific community by the nonscientific
community. The result has been expanding public awareness
and sophistication and a growing need by scientists
to justify the use of public money for scientific research
(and, as a corollary, the increasing need to develop
measurement tools to define the research product). The
major influence on public perception is the public press,
including all mass media. Academic researchers can influence
these perceptions (indeed, they are the source for much
reporting). However, access to mass media is limited
for academic cardiologists and varies regionally. Sophistication
in the means of effective communication by academics
to the nonscientific audience similarly varies and,
as a result, complex and important issues often are
oversimplified, leading to unrealistic public expectations
and misperceptions. Thus, there is great potential for
public education by the academic medical center.
In
each major area of cardiovascular disease, including
coronary artery disease (chronic stable, acute), hypertension
and congestive heart failure and its many causes (including
ischemic, hypertensive, valvular and cardiomyopathic),
extraordinary benefits have resulted from research performed
largely in academic medical centers and involving clinician-investigators,
often as part of multidisciplinary teams fostered and
nurtured within such centers. A few examples should
suffice for illustration. Within the past 25 years,
basic science interdisciplinary research resolved the
hepatic metabolic pathways responsible for endogenous
cholesterol biosynthesis. This discovery enabled cardiologist-basic
scientists to develop pathway-specific pharmacologic
inhibitors of the synthetic reaction. Ten years ago,
other clinician-investigators demonstrated the natural
history-improving benefits of applying the new therapy
in practice; currently, clinical trials are actively
extending the envelope within which net benefits can
be expected from treatment. The result has been major
event reduction associated with our society's primary
cause of "premature" death. Currently, among
patients with known coronary artery disease, approximately
six lives per thousand can be saved each year by application
of the results of this research (2).
Perhaps
the most dramatic developments have been in the area
of heart failure, a condition which affects almost 5,000,000
people in the U.S., with an increase of approximately
500,000 new cases each year. Preclinical and basic science
studies of angiotensin-converting enzyme inhibitors
in heart failure, led and largely performed by clinician-investigators,
quickly were followed by clinical trials which have
revolutionized the treatment of this important cause
of morbidity and mortality. By extrapolation from published
data, application of this research can be expected to
prolong life by at least 1 year, beyond that otherwise
anticipated, for up to 300 of every 1,000 patients with
heart failure (3). More
recent research, again featuring clinician-investigators
in the creation of concepts and shaping of objectives,
has begun assessment of molecular therapy for this condition,
promising added benefit (4).
Indeed, application of the methods of molecular biology
in cardiovascular research has been growing rapidly,
and promises extraordinary future health benefits. Contributions
to the latter process have come from both the academic
and industrial sectors in newly evolving partnership
relations. However, the clinician investigator, the
product of the academic medical center, again has assumed
a critical role in shaping this application of forward-looking
technology.
Comparison
of the performance of academic cardiology with that
of other research sectors is difficult. Currently, private
research entities, though increasing rapidly (see below),
are relatively small and few in number and, thus, cannot
be compared effectively with the large, heterogeneous
entity that is academic cardiology. Industrial biomedical
research primarily occurs in the pharmaceutical and
devices industries. This activity is not directly comparable
to that of academic cardiology because, driven by economic
necessity, industrial research is, by definition, applied.
Academic and industrial research areas are complementary.
Therefore, even in the area of drug discovery at the
basic science level, industrial research largely is
generated in response to the fundamental pathophysiologic
discoveries which result most commonly from research
in academic medical centers. Industrial drug discovery,
in turn, can stimulate and enable further pathophysiologic
understanding, commonly achieved by applying the existing
machinery of academic cardiology with industrial grant
funding. Similarly, although preclinical drug/device
testing can occur in industrial laboratories, much also
is performed under contract by academic centers which
have developed the relevant expertise for multiple purposes.
Finally, clinical testing of drugs and devices requires
effective study design and a cadre of patients, testing
physicians and enabling facilities which already exist
within the context of academic cardiology and would
be expensive to fully duplicate for industrial purposes
(although, as noted in several sections below, inroads
into the position of academic centers are being made
even in this area). A symbiotic relation exists in which
academic resources and expertise are harnessed in perfecting
study design and recruiting, testing and caring for
patients in the context of therapy assessment. However,
as noted below, the growing inefficiency of the academic
medical center in recruiting patients for trials (potentiated
by evolution in medical practice featuring tertiary
center care only for the very sickest patients) and
in obtaining institutional approvals for studies and
contracts is tending to drive industry to non-academic
center partners for performance of clinical trials when
this strategy is feasible. To the problem of academic
center inefficiency is added the problem of overhead
costs which support the academic machinery, also tending
to make the academic center less attractive than the
growing cadre of alternatives for industrial contracts.
It
is clear that important symbiosis and synergy exist
between academic cardiology and industry. However, loss
of the distinction between these entities is inherently
dangerous. Research entails free inquiry which often
fails to support preconceived ideas. Serendipitous findings,
and resulting development of new lines of inquiry, must
allow the capacity for failure. By its structure and
purpose, industry must minimize failed efforts and must
focus its resource allocations toward prespecified applications
of new knowledge. Thus, industry is most efficient if
its work is based on fundamental knowledge which already
has been developed and tested. Redevelopment of the
academic environment within the industrial sector inherently
is uneconomical and is unlikely to occur in the foreseeable
future. Conversely, in the absence of an environment
which fosters unfettered inquiry, new knowledge is unlikely
to develop at the rate our society implicitly has come
to expect. Without the creation of new knowledge, neither
industry nor cardiovascular health will be served.
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