DECISION MAKING AND THERAPEUTIC

STRATEGIES IN CARDIOVASCULAR MEDICINE

C H A P T E R 1  Tools for Assessment of
Cardiovascular Tests and Therapies
Elliott M. Antman, Robert M. Califf, and Niteesh K. Choudhry
INTERPRETATION OF DIAGNOSTIC RESULTS,  1 META-ANALYSIS,  15 COST-EFFECTIVENESS ANALYSIS,  23

CLINICAL TRIALS,  3 Principles of Pooling Studies,  16 Types of Economic Evaluation,  23

Cumulative Meta-Analysis,  16 Methods for Performing a Cost-Effectiveness Analysis,  24
Need for Clinical Trials,  3 Meta-Regression,  17 Other Methodologic Considerations,  26
Clinical Trial Design,  4 Future Trends in Meta-Analysis,  18 Defining When a Therapy is Cost Effective,  29
HOW TO READ AND INTERPRET A CLINICAL TRIAL,  11 How to Read and Interpret a Meta-Analysis,  18 How to Read an Economic Evaluation,  30

Missing Data,  12 COMPARATIVE EFFECTIVENESS RESEARCH,  19 REFERENCES,  30

Measures of Treatment Effect,  12 Methods for Comparative Effectiveness Research,  20
Detection of Treatment Effects in Clinical Trials,  13 Balancing Risks and Benefits,  22

Cardiovascular disease continues to be a major health problem,
estimated to be responsible for about 30% of all global deaths.1
Currently, cardiovascular disease is the leading cause of death in
the United States, and 17% of national health care expenditures
are related to cardiovascular disease.2 The direct medical costs
related to cardiovascular disease in the United States are projected
to increase from $272.5 billion in 2010 to $818.1 billion by 2030;
the indirect costs (lost productivity) are projected to increase from
$171.7 billion to $275.8 billion over the same time period.2 Primary
drivers for these increases in costs include the aging of the popula-
tion, a growth in per capita medical spending, and the epidemic
of such general medical problems as obesity and diabetes. Thus,
selection of therapeutic strategies for patients with cardiovascular
disease must be evidence based and requires consideration of
comparative effectiveness, cost effectiveness, and involvement of
the patient, when capable, in shared decision making.3 The appro-
priate balance of evidence, cost, and patient involvement has not
yet been vigorously established.4-8 Furthermore, there is increasing
recognition that although office practice remains valuable, the
effective practitioner will use a variety of tools to create a “cardio-
vascular team” that can give the patient the best chance of avoid-
ing disease progression and major cardiovascular events. This
more complex environment, one that recognizes the value of team-
work in clinical care, creates a challenging but effective approach
to improving decision making in cardiovascular care.
Therapeutic decision making in the office and hospital practice
of cardiovascular medicine should proceed through an orderly
sequence of events that begins with elicitation of the pertinent
medical history and performance of a physical examination
(Braunwald, Chapter 12). In the ideal situation, a variety of diag-
nostic tests are ordered, and the results are integrated into an
assessment of the probability of a particular cardiac disease
state. Based on this information and on an assessment of the
evidence to support various treatments, a therapeutic strategy is
formulated. In the arena of primary and secondary prevention,
evidence points to the importance of reaching the patient at
home or in the work environment by leveraging Internet-based
technologies—such as e-mail, text messages, and so on—and mid-
level providers. Despite the evolution in our understanding of
these nontraditional settings, the fundamental structure by which
evidence informs choices remains essential. The purpose of this
chapter is to provide an overview of the quantitative tools used to
interpret diagnostic tests, evaluate clinical trials, and assess com-
parative efficacy and cost effectiveness when selecting a treatment
plan. The principles and techniques discussed here serve as a
foundation for placing the remainder of the book in perspective,
and they form the basis for the generation of guidelines for clinical
practice.9 Appropriate application of the therapeutic decision-
making tools that are described and adherence to the guideline
documents based on the tools translate into improved patient
outcomes, an area where cardiovascular specialists have distin-
guished themselves among the various medical specialties.10-12
Interpretation of Diagnostic Tests
A useful starting point for interpreting a diagnostic test is the stan-
dard 2 × 2 table describing the presence or absence of disease, as
determined by a gold standard, and the results of the test.13 Even
before the results of the test are known, clinicians should estimate
the pretest likelihood of disease based on its prevalence in a popu-
lation of patients with clinical characteristics similar to the patient
being evaluated. Because no diagnostic test is perfect, a variety of
quantitative terms are used to describe its operating characteris-
tics, thereby enabling statistical inference about the value of the
test (Figure 1-1). Sensitivity refers to the proportion of patients with
the disease who have a positive test. Specificity is the proportion of
patients without the disease who have a negative test. The probabil-
ity that a test will be negative in the presence of disease is the
false-negative rate, and the probability that a test will be positive in
the absence of disease is the false-positive rate. Other useful terms
are positive predictive value, which describes the probability that
the disease is present if the test is positive, and negative predictive
value, which describes the probability that the disease is absent
when the test is negative. The Standards for Reporting of Diagnostic
1