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2
Review:
Evaluating and Regulating
Biomarker Use
INTRODUCTION
The context within which this study is set has developed from the
contributions of various scientific fields, industries, and government bod-
ies. From toxicology to cardiology, from the food industry to the drug
industry, and from the Food and Drug Administration (FDA) to the fed -
eral courts, biomarkers and the scientific evidence needed to substantiate
their use have been topics of discussion for several decades. Along with a
brief review of biomarker evaluation methods and their uses, this chapter
seeks to describe critical areas of background information so that readers
from different fields can gain a more comprehensive understanding of the
policy and regulatory issues with respect to biomarkers.
Methods for evaluation of biomarkers and surrogate endpoints have
been reviewed successfully and systematically in the recent past (Lassere,
2008; Shi and Sargent, 2009). This chapter will direct the readers toward
appropriate reviews, and it will discuss the evolution of thinking at the
FDA—focusing on the Center for Food Safety and Applied Nutrition
(CFSAN), in particular—regarding surrogate endpoints. It will also dis-
cuss the evolution in thinking in academic and industry communities, to
a lesser extent. The contents of this chapter are as follows:
• se of biomarkers in areas as diverse as scientific research, medical
U
practice, product development, and public health policy
• Use of biomarkers as surrogate endpoints
• valuation frameworks proposed from academia and industry
E
275
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276 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS
• he broader context of biomarker and surrogate endpoint evalua-
T
tion by the FDA, including the legal and regulatory basis for claims
made on CFSAN-regulated products
Examples are included on blood pressure as a surrogate endpoint,
HIV/AIDS drug development, arrhythmia suppression interven-
tions, exercise tolerance in congestive heart failure, and kidney toxicity
biomarkers.
SURVEY OF BIOMARKER USES
Biomarkers have a wide array of uses in a variety of fields. These
fields include medicine, oral health, mental health, nutrition, environmen-
tal health, toxicology, developmental biology, and basic scientific research.
They are used to study the safety and efficacy of interventions, develop
understanding of the mechanisms of disease, make good decisions in
clinical care, and guide the policies that impact public health. Table 2-1
gives a list of several categories of biomarker use.
For the uses in Table 2-1, any biomarker would need to be evalu -
ated to ensure that data supporting the biomarker’s association with
the disease or condition of interest and the analytical validation of the
test are adequate for the proposed use. In situations, however, where
biomarker data will not or is not yet anticipated to be submitted to the
FDA for a regulatory purpose or used by professional societies or other
groups for clinical practice guidelines or other decision-making pro -
cesses impacting public health or the practice of medicine, this may be
an informal process. Ideally, evaluations are already done by clinicians,
product developers, government regulators, professional societies, and
scientists; this report’s contribution is to propose a systematic process
for biomarker evaluation.
Use of Biomarkers and Surrogate Endpoints for Clinical Efficacy
Studies and Formation of Clinical Practice Guidelines
Surrogate endpoints were defined in Chapter 1 and can be found in
several locations in Table 2-1. First, they have been used in approvals of
products or claims for drugs, biologics, devices, foods, and supplements.
This will be discussed further in several subsections of this chapter’s sec -
tion on evolution of regulatory perspectives on surrogate endpoints and
in Chapter 5. Second, they have been used in the formulation of clinical
practice guidelines. As defined by an Institute of Medicine (IOM) commit-
tee in 1990, “practice guidelines are systematically developed statements
to assist practitioner and patient decisions about appropriate health care
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277
APPENDIX B
TABLE 2-1 Categories of Biomarker Use
Use Description
Discovery Identification of biochemical, image, or
other biomarkers associated with a
disease, condition, or behavior of interest;
biomarkers identified may be screened
for many potential uses, including as a
target for intervention to prevent, treat, or
mitigate a disease or condition
Early product development Biomarkers used for target validation,
compound screening, pharmacodynamic
assays, safety assessments, and subject
selection for clinical trials, and as
endpoints in early clinical screening (i.e.,
phase I and II trials)
Surrogate endpoints for claim and Biomarkers used for phase III clinical testing
product approvals and biomarkers used to substantiate claims
for product marketing
Clinical endpoints Biomarkers used as endpoints for clinical
trials that measure how a patient feels,
functions, or survives; for example,
measures of depression, blindness, and
muscle weakness are biomarkers that may
be used as clinical endpoints
Clinical practice Biomarkers used by clinicians for uses such
as risk stratification, disease prevention,
screening, diagnosis, prognosis, therapeutic
monitoring, and posttreatment surveillance
Clinical practice guidelines Biomarkers used to make generalized
recommendations for healthcare
practitioners in the areas of risk
stratification, disease prevention,
treatment, behavior/lifestyle modifications,
and more
Comparative efficacy and safety Biomarkers used in clinical studies looking
at the relative efficacy, safety, and cost
effectiveness of any or all interventions
used for a particular disease or condition,
including changes in behavior, nutrition, or
lifestyle; these studies are a component of
comparative effectiveness research
Public health practice Biomarkers used to track public health
status and make recommendations for
prevention, mitigation, and treatment of
diseases and conditions at the population
level
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278 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS
for specific clinical circumstances” (IOM, 1990). Clinical practice guide -
lines and the systematic reviews that inform them are the subjects for two
current IOM studies;1 the reports are expected in 2011. A guideline regard-
ing treatment of a particular disease may identify target levels for specific
biomarkers. In order to arrive at a recommendation for a particular bio -
marker level, clinical trial and observational data must be evaluated. It is
possible that more trials will measure a particular surrogate endpoint in
addition to or rather than the clinical endpoint of interest. In these cases,
it may be desirable to include data from trials that did not measure the
clinical endpoints of interest in the systematic reviews.
It is useful to mention that professional societies play an essential
role in helping stakeholders understand the best ways to use biomarker-
related information in clinical practice. One way in which professional
societies assist in the understanding and use of biomarker data is through
the promulgation of clinical practice guidelines. The committee recog-
nized that clinical practice guidelines could use the committee’s proposed
biomarker evaluation framework in reaching decisions. Other methods
of rigorous, systematic review, including the Cochrane Collaboration,
may also be valuable in assessing the evidence associated with clinical
practice guidelines. One consideration that bodies involved in the work of
determining the best clinical practice guideline may need to make is that
of cost effectiveness. The committee viewed this topic as being beyond
the statement of task for this study and well studied elsewhere, but the
committee recognizes that comparisons of interventions looking at the
number of quality-adjusted life-years gained through use of an interven -
tion or relative to no intervention are useful.
The IOM recently released a report, Initial National Priorities for Com-
parative Effectiveness Research (IOM, 2009c), which identified six character-
istics of comparative effectiveness research, or CER (Box 2-1). In general,
use of surrogate endpoints in CER would not fulfill the fourth characteris-
tic of comparative effectiveness research, as identified in the report (IOM,
2009c). Quoted below is the report’s description of this characteristic of
CER:
CER measures outcomes—both benefits and harms—that are impor-
tant to patients.
The committee is using the term “effectiveness” in reference to the extent
to which a specific intervention, procedure, regimen, or service does
what it is intended to do when used under real-world circumstances.
1 Standards for Developing Trustworthy Clinical Practice Guidelines (http://www8
.nationalacademies.org/cp/projectview.aspx?key=49125) and Standards for Systematic
Reviews of Clinical Effectiveness Research (http://www8.nationalacademies.org/cp/
projectview.aspx?key=49124).
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279
APPENDIX B
BOX 2-1
Characteristics of Comparative Effectiveness Research (CER)
1. ER has the objective of directly informing a specific clinical decision from
C
the patient perspective or a health policy decision from the population
perspective.
2. CER compares at least two alternative interventions, each with the poten-
tial to be “best practice.”
3. CER describes results at the population and subgroup levels.
4. ER measures outcomes—both benefits and harms—that are important
C
to patients.
5. ER employs methods and data sources appropriate for the decision of
C
interest.
6. CER is conducted in settings that are similar to those in which the inter-
vention will be used in practice.
7. ER has the objective of directly informing a specific clinical decision from
C
the patient perspective or a health policy decision from the population
perspective.
8. CER compares at least two alternative interventions, each with the poten-
tial to be “best practice.”
9. CER describes results at the population and subgroup levels.
10. ER measures outcomes—both benefits and harms—that are important
C
to patients.
11. ER employs methods and data sources appropriate for the decision of
C
interest.
12. CER is conducted in settings that are similar to those in which the inter-
vention will be used in practice.
SOURCE: IOM (2009c).
This can be contrasted with “efficacy,” which is the extent to which an
intervention produces a beneficial result under controlled conditions
(Cochrane, 1971; Higgins and Green, 2008). This implies an important
distinction between much clinical research and CER, in that CER places
high value on external validity, or the ability to generalize results to real-
world decision making. Harms or risks of unintended consequences are
also outcomes of interest, because they influence the net benefits of an
intervention. Including and giving weight to patient-reported outcomes
is particularly important for CER studies in which patient ratings of
effectiveness or adverse events may differ from clinical measures. Finally,
resource utilization may be highly relevant to net benefits when compar-
ing the full clinical course of interventions over time. Cost-effectiveness
analysis is a useful tool of CER, allowing evaluation of the full range
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280 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS
of treatment outcomes in relationship to the difference in costs. Robust
evidence of comparative clinical effectiveness is a building block neces-
sary for resource allocation decisions. Moreover, just as clinical effects
may vary in different settings, costs vary as well, so a given set of cost-
effectiveness results is often not generalizable. (IOM, 2009c)
Comparative effectiveness research is meant to fill gaps in evidence
that prevent comparison of available treatments (IOM, 2009c) with a focus
on outcome measurements that are tangible to the person rather than bio -
markers or putative surrogate endpoints. Occasionally, it may be imprac -
tical for many of these studies to examine clinical endpoints; careful
selection of surrogate endpoints after significant interaction with patient
groups and expert investigators would be necessary. Finally, surrogate
endpoints can be found in public health practice when there is a need to
estimate the health of populations or short-term impacts of longer-term
programs for prevention, treatment, or mitigation of infectious or chronic
diseases when health outcomes important to patients cannot be measured.
For example, reporting to stakeholders about interventions to decrease
diseases and conditions of importance in the population, such as stroke
or heart attack, may be done by measuring and reporting blood pressure
as a surrogate for the desired improvement in health status, although
measuring health outcomes important to patients such as stroke or qual -
ity of life would be preferable as guidance to public health interventions
unless such measures were deemed impractical.
Surrogate Endpoints: Successes
The most widely discussed use of surrogate endpoints is in phase
III clinical studies used to support applications for new drugs, biologics,
and devices and to support claims on foods and supplements. In his pre -
sentation to the committee during its April public workshop, Dr. Robert
Temple of the Center for Drug Evaluation and Research (CDER) at the
FDA outlined the reasons why researchers and clinicians use surrogate
endpoints (Temple, 2009).
These reasons include when the clinical endpoint is rare or takes years
to develop; when the surrogate endpoints seem to be obviously linked
to the clinical endpoint of interest (e.g., tumor size in cancer or mainte-
nance of regular heart rhythm in arrhythmia patients); and when other
treatments exist, to alleviate the difficulties of conducting trials when a
new intervention must be proven as non-inferior to existing treatments.
In addition, although it may be possible to use a clinical endpoint in a
population at high risk for the disease or condition, studying a population
at relatively lower risk using the clinical endpoint may be too burdensome
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APPENDIX B
since the number of subjects required would be very large. Dr. Temple
noted that the idea of a surrogate endpoint is to enable faster, smaller,
more efficient clinical trials that can address urgent needs and facilitate
the advancement of medicine.
Two notable successes of the use of surrogate endpoints are discussed
in the next sections: blood pressure and HIV-1 RNA. The first example
details the history of the evaluation of blood pressure as a surrogate end -
point. It may be surprising to readers that blood pressure as a surrogate
endpoint for cardiovascular disease endpoints was hotly debated for
decades before reaching its current status. Still, there is no broad agree -
ment that blood pressure is a universal surrogate endpoint (Carter, 2002;
Psaty et al., 1996). Even though these examples describe successful use
of surrogate endpoints, important caveats are also described. Dr. Temple
and others have noted surprises and mistakes in the selection and use of
surrogate endpoints, and so several examples of these are discussed after
the sections on blood pressure and HIV-1 RNA.
Blood Pressure
Blood pressure is often looked to as an exemplar surrogate endpoint
for cardiovascular mortality and morbidity due to the levels and types
of evidence that support its use. More than 75 antihypertensive agents
in more than 9 therapeutic classes demonstrate the wide availability of
agents to treat hypertension (Israili et al., 2007). Although new antihy -
pertensive drugs are approved on the basis of blood pressure reduc-
tions, blood pressure’s history as a surrogate endpoint is unusual in that
many drugs used to treat hypertension (thiazides, methyldopa, reserpine,
hydralazine, guanethidine) were approved prior to the FDA’s effective -
ness requirement or the availability of clinical trial data supporting the
impact of blood pressure control on cardiovascular outcomes (Desai et
al., 2006).
The status of blood pressure as a surrogate endpoint for cardiovascu-
lar disease endpoints was debated for decades (Perry et al., 1978). Even as
one of the most well-established surrogate endpoints, an effect on blood
pressure may not fully capture the benefit—or risk—of an intervention.
Although some issues are still outstanding, the benefits of blood pres-
sure control are mostly well understood due to comprehensive epidemio-
logic and clinical trial evidence. Hypertension has been identified as the
most common risk biomarker for cardiovascular morbidity and mortality,
with a World Health Organization report suggesting that hypertension
is the single most important preventable cause of premature death in
developed countries (Ezzati et al., 2002). Data suggest that in the United
States, hypertension is responsible for 35 percent of myocardial infarctions
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282 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS
and strokes, 49 percent of episodes of heart failure, and 24 percent of pre -
mature deaths (Wolff and Miller, 2007). Hypertension affects one in four
U.S. adults, but the majority of those affected remain either untreated or
undertreated in spite of the substantial health benefits gained from mod -
est blood pressure reductions (Wang and Vasan, 2005).
Epidemiological, clinical trial data Williams (2005) suggested that the
blood pressure–cardiovascular outcomes relationship is substantiated by
one of the strongest evidence bases in clinical medicine. Epidemiologic
studies consistently demonstrate the relationship between blood pressure
and cardiovascular mortality and morbidity, including one meta-analysis
of nine studies that demonstrated an association between diastolic blood
pressure and coronary heart disease and stroke in 420,000 subjects (Mac-
Mahon et al., 1990). Observational studies have also demonstrated the
robustness of blood pressure’s relationship to heart disease in adults;
despite different assessment parameters (systolic alone, diastolic alone, or
systolic and diastolic), the relationship is maintained (Desai et al., 2006).
This relationship has also been confirmed in diverse populations, includ -
ing different genders, adult age groups, and race/ethnicities. In children,
this relationship does not hold (Brady and Feld, 2009).
Both placebo- and active-controlled clinical trials conducted in the
past three to four decades have demonstrated that pharmacologic reduc-
tions in blood pressure reduce cardiovascular mortality and morbidity
(Desai et al., 2006). While earlier trials compared hypertension agents
against placebo, the growing evidence base supporting the benefit of
hypertension therapy necessitated head-to-head trials comparing two
or more agents, which reduced power of the studies and required much
larger numbers of patients to see an effect (Williams, 2005). Many dif -
ferent therapeutic agents—including diuretics, beta blockers, angioten -
sion converting enzyme (ACE) inhibitors, calcium channel blockers, and
angiotensin receptor blockers—are approved to lower blood pressure.
Effects of blood pressure-lowering drugs Impact on blood pressure may
or may not capture an intervention’s entire risk–benefit balance. Different
classes of agents, or even agents within a specific class, may have mul -
tiple effects, one of which is lowering blood pressure (NHLBI Working
Group, 2005). For example, ACE inhibitors are known to have at least 10
pharmacologic effects (Borer, 2004). This notion has generated trials test -
ing whether agents have beneficial effects that go beyond blood pressure
lowering. ALLHAT (Antihypertensive and Lipid Lowering Treatment to
Prevent Heart Attack Trial) compared the efficacy of four different drug
classes (a calcium channel blocker, an ACE inhibitor, an alpha adrenergic
blocker, and a diuretic) for initial therapy of hypertension. Study results
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283
APPENDIX B
demonstrated that three classes of drugs (calcium channel blocker, ACE
inhibitor, and diuretic) could not be distinguished for the primary end-
point, coronary heart disease (CHD) mortality and non-fatal myocardial
infarction, but the lower cost diuretics were superior in regard to second -
ary outcomes and should be the preferred first step therapy (ALLHAT
Officers and Coordinators, 2002). The alpha adrenergic blocker arm of
the trial was dropped because of the significantly higher incidence of
combined cardiovascular events in the alpha adrenergic blocker arm com-
pared to the diuretic, including a two-fold relative risk of congestive heart
failure compared to the diuretic (ALLHAT Officers and Coordinators,
2000).
Other conclusions have also been drawn from these large, prospective
head-to-head comparison trials; some investigators suggest that it is the
blood pressure reduction, rather than the specific drug used, that confers
cardiovascular benefit (Williams, 2005). In an analysis of 147 random-
ized trials, investigators found that all classes of blood pressure-lowering
drugs have similar effects in reducing coronary heart disease events and
strokes for a given level of blood pressure reduction, with the exception
of an extra protective effect of beta blockers administered shortly after
myocardial infarction and minor protective effect of calcium channel
blockers in stroke (Law and Morris, 2009). Although there is still some
ambiguity about the use of differing blood pressure agents, the fact that
pharmacologically distinct agents have directionally similar effects on
cardiovascular outcomes has provided more support for the use of blood
pressure as a surrogate endpoint for coronary heart disease and stroke.
Regulatory use of blood pressure as a surrogate endpoint The consis-
tent demonstration that diverse blood pressure-lowering agents confer
cardiovascular benefits, as well as the substantial epidemiological data
linking hypertension to cardiovascular events, provides the basis for the
FDA’s use of blood pressure as a surrogate endpoint (Desai et al., 2006;
Temple, 1999). However, clear guidance on the use of surrogate endpoints
within the FDA is lacking because the Food, Drug, and Cosmetic Act does
not specifically state which endpoints—or criteria—can be used for drug
approval. Through case law, the FDA has the authority to deny approval
of a drug on the basis of its effect on the surrogate endpoint if the surrogate
endpoint’s clinical value is unknown.2 In 1992, FDA regulation provided
a new method for drug approval on the basis of effects on a surrogate
endpoint, called accelerated approval, for serious or life-threatening con -
ditions without available therapy. The regulation stated that drugs could
be approved on the basis of surrogate endpoint data if it “is reasonably
2 Warner-Lambert v. Heckler, 787 F.2d 147 (3rd Cir. 1986).
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284 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS
likely, based on epidemiologic, therapeutic, pathophysiologic, or other
evidence, to predict clinical benefit”3 and required confirmatory clinical
evidence. The regulation also referenced “well-established” surrogates on
which drug approval had been based, but did not define well-established
endpoints. Temple (1999) noted that “well-established” surrogates would
need to be more than “reasonably likely” to predict benefit.
Despite the lack of clarity in the regulations concerning surrogate
endpoints, the FDA accepts surrogate endpoints for drug approval and
as the basis for authorized health claims. However, different divisions
and centers within the FDA accept different surrogate endpoints. For
example, the Cardio-Renal Division within the CDER accepts blood pres -
sure reduction as a surrogate endpoint for cardiovascular event reduc-
tion, but requires direct clinical benefit measurement for other endpoints,
while the Metabolic-Endocrine Division also accepts LDL-C lowering as a
surrogate endpoint for cardiovascular events (Borer, 2004). The Metabolic-
Endocrine Division also accepts use of glycosylated hemoglobin level and
blood glucose control as surrogate endpoints for diabetes control (Borer,
2004). Even so, the FDA has recognized the inadequacy of small six-month
trials that address effects of type 2 diabetes mellitus treatments on HbA1c,
and now the FDA requires large-scale randomized cardiovascular safety
clinical endpoint trials be conducted pre- and post-approval.
Within CFSAN, blood pressure is recognized as a surrogate end-
point for hypertension (FDA, 1999). Hypertension is considered a disease-
related health condition. As discussed earlier, hypertension—high blood
pressure—is recognized as a strong risk factor for cardiovascular disease.
CFSAN has authorized a health claim for low-sodium foods based on the
surrogate endpoint–disease-related condition relationship, stating either
“diets low in sodium may reduce the risk of high blood pressure, a disease
associated with many factors” or “development of hypertension or high
blood pressure depends on many factors. [This product] can be part of a
low sodium, low salt diet that might reduce the risk of hypertension or
high blood pressure.”4
HIV Drug Development
One of the motivations for the earliest efforts at surrogate endpoint
evaluation arose from the acute need for effective therapeutics early in the
HIV/AIDS epidemic. The early trials of anti-HIV therapies used progres -
sion to AIDS or death as the clinical outcome measures. These studies
could be short in some settings, like those in which the effects of the
3 21 C.F.R. § 601 (2008).
4 21 C.F.R. § 101.74 (2009).
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APPENDIX B
intervention were large and participants had advanced disease (Fischl et
al., 1987; Hammer et al., 1997). Studies could also be short when they were
large enough so that only a small percentage of patients who progress to
advanced disease drove the principal finding (Volberding et al., 1994).
However, the latter type of study could produce misleading results in
that a small number of patients destined to progress quickly might ben -
efit from an intervention, like AZT monotherapy, while an even larger
number might experience no benefit and even positive harm following
the conclusion of the study, because of factors like the development of
resistance to the drug under study and others with similar mechanisms
of action. Such concerns underscored the need for a more rapid means of
evaluating the benefit of antiviral therapy that might reflect risk or benefit
to a larger proportion of the study population more rapidly.
Early in the AIDS epidemic, it was observed that clinical disease
progression was associated with a decline of CD4+ T-lymphocytes (CD4
cells); in the 1990s, a virologic measure that both responded to ther-
apy and predicted outcomes was developed (HIV-1 RNA). The earliest
approval of a drug based on a biomarker—didanosine was approved in
1991—used CD4 cell count; however, the development of measurement
of plasma HIV-1 RNA by polymerase chain reaction (PCR), which made
a direct measurement of viral replication possible, rapidly became the
standard endpoint in HIV clinical trials. In the mid-1990s, representatives
from industry, drug regulatory agencies, and academia sought to formally
evaluate CD4 cell count and HIV-1 RNA as surrogate endpoints for dis-
ease progression in clinical trials and in patient management (Hughes et
al., 1998).
To evaluate HIV-1 RNA and CD4 cell count as surrogate endpoints,
the HIV Surrogate Marker Collaborative Group, a group involving stat-
isticians and clinicians from pharmaceutical companies and government-
funded cooperative clinical trials groups, was formed. The HIV Surrogate
Marker Collaborative Group undertook a meta-analysis of clinical trials to
evaluate treatment-mediated changes in HIV-1 RNA and CD4 cell count
as surrogate endpoints (HIV Surrogate Marker Collaborative Group,
2000). The meta-analysis found that HIV-1 RNA and CD4 cell count have
independent value as prognostic biomarkers. However, the meta-analysis
also found that short-term changes in the values of these biomarkers were
not adequate surrogate endpoints for determining the impact of an inter-
vention on long-term clinical endpoints such as progression to AIDS and
death (HIV Surrogate Marker Collaborative Group, 2000). Their analysis
also showed that changes in HIV-1 RNA explained only about half of the
benefit of treatment. However, these results mostly reflected the experi-
ence of patients on drug regimens that were not capable of suppressing
most patients’ viral loads below levels of assay detection.
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328 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS
Each of these heuristics and biases are explained in the referenced
paper (Tversky and Kahneman, 1974). An example of insensitivity to
probability bias, also known as neglect of probability bias, is when a
person chooses to eat a nutrient or other substance that has been shown
in observational studies to be associated with a reduced risk of disease,
while ignoring the fact that this research alone does not confirm a sub -
stance’s causal connection to a reduced risk of disease. Because these
biases are well known, some may try to take advantage of them to mislead
consumers.
Cognitive biases of healthcare professionals in health-related decision
making have been studied in the context of emergent (Pines, 2006), acute
(Aberegg et al., 2005; Freshwater-Turner et al., 2007), and chronic health-
care settings (Gruppen et al., 1994; Lutfey and McKinlay, 2009; Redelmeier
and Shafir, 1995; Roswarski and Murray, 2006), while cognitive biases of
patients have been evaluated in regard to illnesses such as myocardial
infarction (Khraim and Carey, 2009) and cancer (Han et al., 2006).
Efforts by professional societies can help physicians, dietitians, and
other healthcare practitioners be aware of information gaps and common
cognitive biases when helping their patients or clients make decisions
about their health care. With this knowledge, strategies can be developed
and disseminated. In situations where the public and health professionals
need to make decisions in the absence of complete, definitive evidence,
decision makers need to be able to access balanced, non-misleading data,
or they will be likely to make systematic errors in their thinking.
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